All posts by kpowers

Inside the O’Briens

 

Courtesy of Amazon.com

Following her great success with Still Alice and Alzheimer’s disease, neuroscientist and author Lisa Genova attempts to accurately portray the disease experience of a Huntington’s disease (HD) family in her latest novel, Inside the O’Briens.

Unlike most media outlets, Genova goes to great lengths to understand the disease, both medically and socially, through interviews with HD researchers, clinicians and family members. Whether it’s describing the deterioration of the disease or explaining job discrimination, Genova succeeds in portraying the real HD disease experience.

Description^

Inside the O’Briens follows the story of Joe O’Brien, a middle age Boston police officer. He is married to Rosie O’Brien, with whom he has four children: Patrick, JJ, Meghan and Katie, all of whom still reside in the same triple-decker house in Charlestown, Massachusetts. Joe lives a content life and has very little problems within his family, despite a stressful job as an active duty police officer.

However, Joe and his family begin to notice changes in his behavior and movements. Joe is quick to anger and begins to loose his coordination. His wife, Rosie, convinces Joe to seek medical help. Sadly, he is diagnosed with Huntington’s disease. This news comes to a shock for Joe, whose family never acknowledged a history of the disease, until he re-considered the symptoms of his mother’s “alcoholism” many decades ago.

The story outlines the challenges Joe’s family must face as they not only navigate the disease progression of their father, but the fact that all four siblings have a 50% chance of inheriting the disease. The book is a challenging read, accurately portraying the unique problems HD families all over the world face.

Genetic Testing^

Genetic testing, in addition to reproductive strategies, is one of the most controversial aspects of the HD experience. Despite the presence of a gene test, estimates show only 5-10% of all at-risk individuals choose to undergo predictive genetic testing (Oster et al., 2011 ). These statistics sometimes frustrate clinicians, leading to rash or coerced genetic testing decisions between the patient and doctor.

Rosie, Joe’s wife, accompanies Joe on a consultation with neurologist Dr. Hagler. Rosie notes the various movement symptoms Joe does not notice due to a lack of proprioception, or the ability to detect one’s body position. Dr. Hagler requests information regarding Joe’s family history and discovers that his mother was hospitalized for “alcoholism.” She also has Joe perform several neurological tests without explaining the reasoning behind these tests. Despite Joe’s insistence that he is just having a knee problem, Dr. Hagler suddenly diagnoses Joe with Huntington’s disease, but admits they should get an MRI and genetic testing to confirm her diagnosis (76-108).

Without any consent or transparency, Dr. Hagler diagnoses Joe with a devastating neurological disease with no counseling or explanation, causing great psychological stress to the family. Joe is furious that a medical professional could be so irresponsible in her prognosis:

“Huntington’s. It’s pure malarkey, and Joe won’t give it any stock. Police officers deal in facts, not speculation, and the fact is, this doctor threw out this big, scary medical word without having done any real medical tests, without knowing a damn thing. It was an offhand, irresponsible remark. It’s practically malpractice, to put a word like that out there, into their innocent heads, with no facts to back it up. It’s complete bullshit is what it is” (84).

Genova does an excellent job of highlighting the ways in which professionals can negatively impact a diagnosis experience. For families unaware of a history of Huntington’s disease, an abrupt clinical diagnosis with little explanation or consent can be harmful.

Furthermore, a diagnosis of Huntington’s disease can be devastating because of the implications it can have for younger generations. In the case of Joe’s family, his diagnosis means that his four children also must acknowledge they each have a 50% chance of inheriting the disease.

Genova highlights the tensions this statistic can cause among family members, especially when it comes to making the decision to test. In one section of the book, Genova creates a dialogue between the four siblings regarding their decision to test. The brothers, JJ and Patrick, are frustrated by the fact that they must undergo a long genetic testing process to find out if they have inherited the disease. Patrick refuses to get tested as he does not want to do any of the counseling.

JJ decides to test as his wife, Colleen, is pregnant with their first child. Meghan, one of the sisters, asks JJ if he and Colleen would have an abortion if he tested positive for the disease and so did the baby. [For more information on fetal testing or family planning in general, click here.] The stress is palpable. JJ doesn’t have an answer to his sister’s question.

The siblings discuss the fear that they’ve already started exhibiting symptoms. Meg, a ballet dancer, believes she’s messing up more in her routines. It is not unusual for those at risk to self-identify or diagnose based off behaviors that may or may not be related to Huntington’s disease. Her siblings try to reassure her that it is nothing.

At the end of the conversation, JJ and Meg decide to pursue testing, Patrick will not, and the youngest, Kate, is undecided.

Kate decides to pursue the genetic counseling process. She meets with Eric Clarkson, a genetic counselor. She does so after an upsetting neurological exam by Dr. Hagler, the same woman that analyzed Kate’s father’s movements. At the end of the exam, Dr. Hagler tells Kate that everything looks normal, leaving Kate with mixed emotions. She’s spent the last few weeks studying herself, trying to identify signs of the disease. Now she can finally stop. In Kate’s words: “That neuro exam was like surviving fifteen rounds in a boxing ring. She’s been declared the winner, but she still got knocked around” (162).

Eric takes over for Dr. Hagler to discuss genetic testing with Kate, asking her about the uncertainty surrounding her decision to test. Katie admits to Eric that she believes she has the gene because she looks like her dad’s mother. Eric reassures her that physical resemblance has nothing to do with HD inheritance. He uses this misconception as an opportunity to go over basic genetics, explaining DNA, chromosomes, and genes.

Additionally, Eric asks Kate to articulate what life would be like if she tested negative (“biggest relief ever”) and if she tested positive, along with her siblings testing positive. Kate says she “wouldn’t jump off the Tobin [bridge]” (168). Kate is getting increasingly uncomfortable with the intensity of the conversation. She grows increasingly impatient and tries to ascertain the reason for this “interrogation.”

Eric explains to her that he will not deny her the test. However, he says, “we want you to understand what you’re getting into and have the tools to deal with it. We feel responsibility for how you’re going to react” (171). He says that Kate can come back in two weeks to get the test or continue to visit with each other until she feels ready. He emphasizes that he will deliver her results to her in-person, and not over the telephone, a common best practice of genetic testing.

Overall, Eric Clarkson does an excellent job explaining the disease to Kate, as well as the emotional implications of genetic testing.

Family Members with HD^

Many children from Huntington’s disease families must reconcile the fact that they have watched a parent suffer from a long, debilitating illness. This experience can cause trauma and psychological stress, especially as many of these children must also face their own personal realities of the disease.

Joe is no exception:

“But while he’s been doing his best to avoid falling down the dark, muddy rabbit hole of Huntington’s disease, he has been thinking a lot about his mother. Joe stops turning the screwdriver and runs his index finger over the scar by the outside corner of his left eye…His mother threw a potato masher across the room…Joe likes to believe that the scar by his eye is the only thing he got from his mother, a single souvenir of her madness” (85).

The disease can often strip individuals of their identities as well:

“The woman in that bed would never be able to read or sing or smile at him again. The woman in that bed was nobody’s mother” (87).

Grappling with Huntington’s disease can be a taxing feat considering the fact that multiple generations often have to deal with its consequences simultaneously. This burden is particularly evident when Joe must tell his children that they all have a 50% chance of inheriting the disease, in addition to the risk it poses to any children they plan on having. As described on page 122, the four siblings have great difficulty comprehending the magnitude of the situation. For JJ and his wife Colleen, it is far too real, as they reveal that Colleen is pregnant.

As is revealed later in the text, JJ tests positive for the faulty gene, meaning his child is now also at-risk for the disease. He and Colleen decide to keep the baby, despite the risk. As stated on page 202, “Joe prays everyday that the baby is healthy.” Joe also acknowledges that once the baby is born, the child cannot be tested until he or she makes the decision to do so, which at minimum is 18 years away, meaning he may never know whether or not it passes on to the next generation.

Employment^

Unemployment is perhaps one of the most difficult transitions for many HD patients living in their working prime. Joe, a police officer, must face this transition earlier than others due to the high intensity and dangers involved in his job. Before losing his position on the force, Joe is accused of directing traffic while drunk, a common misconception of individuals with HD. He had not yet revealed his diagnosis to anyone outside his closest circles. However, after several complaints and rumors, Joe must finally disclose his disease status to his boss. Joe must grapple with the fact that, at best, he may keep his job at a desk. Otherwise, his future on the force does not look promising (234).

Genova uses this crisis in Joe’s life to explain the Genetic Information Non-Discrimination Act (GINA). This piece of legislation “makes it illegal for employers to terminate an employee based on genetic information” (247). However, an employer retains the right to fire somebody if that individual poses a safety threat or cannot do his or her job effectively. This caveat means Joe cannot be protected by GINA, but perhaps this information can help other readers.

Suicide^

Suicidal ideation is one of the most pressing issues in the Huntington’s disease community. It is a difficult topic to discuss, but a matter that must be addressed in order to make progress and educate communities touched by the disease.

When Joe is accused of drunk policing, his co-worker mentions that “this time of year is brutal” (244). The community has seen three suicides in the month of January. Joe imagines the various ways these individuals may have killed themselves. The last one he imagines: “a cop eats his gun” (244). He then thinks this “last one is how he’d do it, if suicide were his plan.”

Joe spends several scenes of the book contemplating his death. Chapter 29 begins with the sentence, “The gun is still his plan.” Rosie dissuaded Joe from taking his own life before, but his ideation is still frequent. Joe finds himself obsessively checking his draw for the gun, just in case he decides he needs to use it. Katie, his youngest, is the one that has the most effective impact on Joe leaving his “perfect plan behind.”

The passage reads as follows:

“’We don’t know anyone else with HD. You’re the only example we have. We are going to learn how to live and die with HD from you, Dad’…

It’s the perfect plan. He’ll be teaching them the human thing to do, the victorious way out. The gun. He should check the gun” (273).

Through his conversation with Kate, Joe realizes the importance of his presence to his family. He decides that, personally, it would be better for him to not choose suicide.

Everyday Challenges^

While suicide and job loss often grab the headlines for HD communities, sometimes the everyday challenges are the hardest.

Joe describes his everyday encounter with strangers. Due to a lack of proprioception, or the ability to sense one’s body position, Joe can only perceive his movements “through the mirror of the guarded, unforgiving stares of strangers” (212). Otherwise, he cannot tell that his body is moving. Joe describes the feeling of having strangers stare at him, trying to pin him into categories like drunk, mentally impaired, harmless, violent, deranged. As Joe states, he is “horrifying, unacceptable, and then invisible” to these strangers.

Furthermore, Joe explains his symptoms by calling himself his own “stuntman.” With the combination of proprioception and anosognosia, he is unaware of the placement of his body. Not only does this cause him to move unexpectedly, but often with more force than intended. He also finds himself hard pressed to control extreme mood swings, often towards anger, which often makes him feel guilty as it can be extremely traumatizing for his family.

Joe also describes his challenges with the limited number of drugs on the market. While Tetrabenazine helps control his chorea, Joe must take less of it as it increases his suicidal ideation. The constant management of drugs to control for various symptoms of HD can be exhausting.

One of the greatest mechanisms for coping with the daily challenges with the disease is a support system. When Joe attends a baseball game with his friends, he must face the unforgiving glares of strangers bewildered by his movements. However, his friends and family are there to support him, melting away the attempts of others to judge him. As the Red Sox win the game, Joe “takes a moment, wanting to remember this, the joy of the win, the beers and pizza, the electric energy of the crowd, a night at Fenway with his best friends and his two sons. His seat ain’t empty yet. And tonight, he enjoyed every wicked awesome second of it” (330).

Conclusion^

Lisa Genova provides readers with one of the most comprehensive looks into the lives of those affected by Huntington’s disease. She touches on issues like Juvenile Huntington’s disease, insurance, genetic testing, drugs, and more, all the while providing and engaging story for readers from all walks of life. Genova does an excellent job proving she did her research. Whether it was speaking with HD families, connecting with the Huntington’s Disease Society of America or grilling HD researchers, she makes every effort to accurately portray one potential disease experience at both the family and the individual level.

For Future Reading^

Oster, Emily, Ira Shoulson, and E. Dorsey. Optimal expectations and limited medical testing: evidence from Huntington disease. No. w17629. National Bureau of Economic Research, 2011.

KP 2015

 

 

 

 

More

HD in Scrubs

In the season 8 finale of Scrubs, a popular medical TV show, one of the doctors diagnoses a 70-year-old woman with Huntington’s disease. While manifestation of the disease is more common during middle age, presenting symptoms later on is possible. JD, the physician on the show, does his best to explain the disease in a manageable, understandable way without neglecting to mention that the patient’s son, Mr. Stonewater, is also at risk for this genetic disease. JD offers Mr. Stonewater the genetic test that would reveal whether or not he had inherited the same faulty gene as his mother. Mr. Stonewater asks for some time to consider his options.

JD goes through the rest of his day fazed, as he knows how devastating the disease is and how difficult a decision it is whether or not to pursue genetic testing. When Mr. Stonewater informs JD that he does not want to take the test, JD respects his wishes.

Script

Background:

The son, Mr. Stonewater, had told JD that his mom wasn’t acting like herself. When JD tries to examine her she lashes out and accuses him of trying to attack her. JD comes back later with a diagnosis.

Dialogue:

Stonewater: She has Huntington’s disease?

JD: It’s a degenerative brain disease, causes you to lose control of your movement and mental ability. It can also change your personality like with your mom.

Stonewater: So what do we do?

JD: Unfortunately, there’s no cure. Eventually it will take her.

Stonewater: Oh geez.

JD’s internal monologue: Sometimes, you just have to barrel through no matter how much it sucks.

JD: And Mr. Stonewater, Huntington’s is caused by a faulty gene. And since your mother has it, you have a 50/50 chance of having it too. We can test you for it if you want.

Stonewater: If we find out that I have it early on, are there any treatment options?

JD: Nothing substantial yet. I can only tell you if you have it, can’t even tell you when the disease would hit you if you do have it. Could be in your 70’s like your mom or…

Stonewater: Could be sooner.

JD: Could be sooner. I’m so sorry.

Stonewater: Can I have a few minutes?

Next scene:

JD internal monologue: I’m so bummed about Mrs. Stonewater that I totally spaced and forgot what was wrong with Benjamin here. Is he the one with broken ribs? Nope. Maybe he’s the guy with sinus polyps. I don’t think there’s any polyps but he definitely has some oily skin issues. I should turn him on to that awesome apricot scrub I stole from Elliott. Come on, focus!

Next scene:

In an argument with Elliott, a fellow hospital employee and JD’s girlfriend

JD: NO, Elliott. I’m upset because Huntington’s disease sucks, Dr. Cox is a jerk and I’m such a crappy doctor I just got dumped by a patient. And nobody but you and Turk care that I am leaving.

Later, JD encounters the patient in the hallway as he explores the challenges of offering the genetic test for Mr. Stonewater.

JD’s internal monologue: Sometimes it’s deciding that you don’t want to know if you have a fatal disease.

Stonewater: Dr. Dorian, I decided not to take that test.

JD: Ok.

(JD walks away from the patient in a haze of his own internal monologue)

End scene

In this case, it is unusual for a doctor to recommend the genetic test without explaining the formalities that accompany it—genetic counseling, psychiatric and neurological evaluations as well as a blood draw. These aspects of genetic testing, along with the risks—discrimination, insurance spikes, depression, etc.—were probably not included in this episode due to the nature of the show (entertainment versus documentary). We would like to clarify that doctors should always explain the full process of genetic testing before offering it, especially if someone has only been recently introduced to the disease. Other than the exemption of these facts, JD does not misinform Mr. Stonewater about his genetic risk or the fate of his mother and explains the facts clearly and succinctly.

However, as you can see from JD’s internal monologue, genetic testing can be a complicated decision even for the medical professionals. Genetic counselors, neurologists, and psychiatrists all work together to determine a patient’s ability to handle an HD genetic testing. They must consider the ramifications of the test and the results potential impact on the health of the patient, which might include risk of suicide or depression. These professionals often face great stress upon the reveal of the results, as they are all too aware of the implications of the test. We can see the type of strain this places on JD as he emphasizes with Mr. Stonewater’s tough predicament.

Within the context of a medical drama TV series, this episode overall accurately portrays the difficulties for the patient, the family, and the physician involved in dealing with the realities involved in dealing with the delivery of an HD diagnosis.

KP 2014

 

 

 

More

HD in ER

*ER is a medical drama television series*

In the Season 9 Episode “Insurrection,” a late-stage Huntington’s disease (HD) patient is rushed into the Emergency Room (ER). The ER is in chaos during this episode, as doctors and nurses walkout to protest unsafe working conditions. Inside the hospital, the absence of staff makes it easy for the desperate mother of the patient to switch off the ventilator that is supplying life to her son. To her, this action is probably one of mercy, as she knows her son’s life will never get better.

 

When Dr. Lewis discovers what the mother has done, she decides not to press murder charges in order to protect the mother from prison.

 

Background: The ER receives a patient with end stage Huntington’s disease. He fell out of bed and potentially broke his hip.

ER doctor: What do we know?

Another doctor: Huntington’s, starts in your early 30’s and 40’s starts with your emotional ability and depression, leads to a progressive loss of motor control and loss of cognitive function.

 

Later: The patient is having sudden troubles unrelated to his hip. His mother is there. She apologizes to him for the quality of the nursing home and says it was the best she could find. She doesn’t have much money to pay for quality care. The mom keeps pointing out how much her son is suffering and begs the doctors to help him. Later on, he chokes on vomit and they want to put in a tube despite scars in his pathways from a ventilator a few months ago. The mom asks “That’s it right? When you put that tube in, it’s not coming out, right?”

 

Later: The patient needs to go to the operating room. The mom asks Dr. Susan Lewis if she knows what it is like to watch someone die for 25 years.

 

Dialogue:

Mother: It’s what I did with his father every day. I loved the man, but I hated what it did to him.

Doctor Susan Lewis: I can refer you to another nursing home. I don’t know what you are paying now.

Mom: He was a singer, didn’t you know? An opera singer, a tenor? When he sang, it was the most beautiful sound in the world. I prayed it would pass him over. When he got to be 29, I thought, my God maybe we got lucky. Then he started having trouble at work. Forget things and when he talked sometimes he was hard to understand. And of course…of course he couldn’t sing anymore. It just takes everything away. Everything.

 

Next scene: During the walk out in which many of the doctors are protesting unsafe working conditions, the mother turns off her son’s ventilator. Doctor Lewis comes back in and turns on the ventilator to prevent suspicion. She hides the patient’s true cause of death in order to protect the mother.

 

ER is intended to be a medical drama. In its effort to emotionally influence viewers, ER often neglects to explore the ethical implications of the characters’ actions. In this episode a distraught, desperate mother watches her son suffer as the doctors attempt, not to cure or treat his symptoms, but extend and hopefully improve his quality of life.

 

The mother has been a caregiver for a long time. She had to care for her husband until he passed away, and her son as well. She expresses the difficulty of watching a loved one lose the ability to do things he or she enjoys like opera singing, in her son’s case. This episode shows the challenges facing caregivers and the emotional burden resulting from decades of caring for those affected by the disease.

 

This episode highlights end-of-care controversies for HD patients such as death with dignity or assisted death. There are currently only three states that have Death With Dignity Laws–Washington, Vermont and Oregon. These laws allow mentally competent, terminally ill adult state residents to hasten death using prescribed euthanasia medication.1 This choice is complicated one for the HD community; Qualifications such as “mentally competent” might be defined in various ways among physicians, patients, and family members as HD does cause cognitive and psychiatric issues.

 

Suicide or assisted suicide are major issues in the Huntington’s disease community. In fact, suicide is often the leading cause of death among those who have inherited the mutant gene. Because of the gravitas of these actions, it is extremely important that health care providers do all they can to understand the psychological impacts the disease has on the individual as well as family members. In addition to health care providers, caregivers and family members should be well-educated on what to do if their loved one is experiencing suicidal ideation.

 

Dr. Lewis did not follow proper procedure upon discovering what the mother had done. She altered the cause of death to avoid focusing any suspicion on the mother. Dr. Lewis neglected to follow protocol in order to protect the mother from legal ramifications. While this might be an exception a doctor would make in a TV drama, it is not something that should be expected of any physician. Patients and caregivers should have an open dialogue with primary care doctors to discuss end-of-life options such as “Do not resuscitate” (DNR) or preventing the use of feeding tubes.

 

The subject matter in this episode of ER is very heavy. It highlights the burden on caregivers and why family members might consider options such as assisted suicide. If you are a Huntington’s disease caregiver, you can find resources and support networks by visiting hdsa.org/living-with-huntingtons/family-care/caregivers.html

 

Works Cited

  1. “Defend Dignity. Take Action.” Death with Dignity National Center. N.p., n.d. Web. 11 Aug. 2014.

KP 2014

More

Breaking Bad

Breaking Bad is a popular U.S. crime drama television series that aired from 2008 to 2013. The main character, Walter White Jr., discovers that he has inoperable lung cancer and decides to sell methamphetamine in order to secure his family’s financial future when he passes.

In an episode titled Salud, Walter’s son is celebrating his 16th birthday. Unfortunately, Walter is less than able to celebrate with him due to various self-inflicted medical problems. The next morning, he sits his son down to tell him about a childhood memory that has always haunted him.

The Dialogue

Walt: My father died when I was six. You knew that right?

Son: Yeah.

Walt:

He had Huntington’s disease; it destroys portions of the brain, affects muscle control, leads to dementia, it’s just a nasty disease. It’s genetic. Terrified my mother that I might have it so they ran tests on me when I was a kid, but I came up clean.

My father fell very ill when I was four or five. He spent a lot of time in hospitals. My mother would tell me so many stories about my father. She would talk about him all the time. I knew about his personality, how he treated people, I even knew how he liked his steaks cooked, medium rare, just like you. I knew things about my father. I had a lot of information. It’s because people would tell me these things. They would paint this picture of my father for me. And I always pretended that that was who I saw too, who I remembered. But it was a lie. In truth I only have one real actual memory of my father.

It must have been right before he died. My mother would take me to the hospital to visit him and I remember the smell in there. The chemicals: it was as if they used up every single cleaning product they could find in a 50 mile radius, like they didn’t want you smelling the sick people. Oh, there was this stench of Lysol and bleach, I mean, you could just feel it coating your lungs. Anyway, there lying on the bed, is my father. He’s all twisted up. My mom, she puts me on her lap, sitting on the bed next to him so I could get a good look at him, but really…he just scares me. And he’s looking right at me, but I can’t even be sure that he knows who I am. And your grandmother is talking, trying to be cheerful, you know, as she does. But the only thing I could remember is him breathing. This rattling sound like if you were shaking an empty spray paint can…like there was nothing in him.

Anyway, that is the only real memory that I have of my father. I don’t want you to think of me the way I was last night. I don’t want that to be the memory of me when I am gone.

Son: Remembering you that way wouldn’t be so bad. The bad way to remember you would be the way, the way you’ve been this whole last year. At least last night you were real, you know?

————————————————————————————————————————-

While it is great that Breaking Bad is introducing millions of viewers to Huntington’s disease, there is always a risk of misinformation or stereotyping in entertainment media. In this episode, the most glaring mistake is the comment Walter makes regarding his genetic testing for the disease.

Walter stated that his mother was so scared of Walter Jr.’s at-risk status; she had tests run on him when he was six years old. However, the historical timeline is skewed. In order to test for Huntington’s disease prior to symptom expression, an individual must undergo genetic testing. However, predictive genetic testing was not available until 1993 after Nancy Wexler’s team discovered the location of the gene that causes Huntington’s disease. As Walt is middle-age, it is not possible that he was expressing symptoms of Juvenile Huntington’s Disease as individuals with this disease often don’t live beyond their 20’s.

In the episode, Walter notes that he tested negative for the disease when he was a child. However, genetic testing had only been available for about 15 years. If Walter had been able to test before his sixth birthday, he would have to be no older than 21 years old, assuming this episode took place in 2008. Walter is a middle-age adult with a 16-year-old son so there is no way genetic testing would have been possible at the time he said it was.

Forgetting, for a moment, that genetic testing was not feasible when Walter was a child, coercive genetic testing is another topic that was glossed over quickly within the dialogue. In the United States, it is strongly recommended that genetic counselors only test individuals over 18 years old or legal adulthood. There are a variety of reasons why this recommendation is in place. In respect to Breaking Bad, it would prevent parents, such as Walter’s mother, from testing at-risk, non-symptomatic children without their legal consent. Children are thus protected from discrimination from their parents (intentionally or not) as a result of their test outcomes. Additionally, it is the affected individual’s right to decide if he or she wants to know, which is why parental coercion is highly discouraged.

In this episode, it is clear that Walt has traumatic memories of his father. Unfortunately, for many children in Huntington’s disease families, childhood can be filled with hardship as many parents become symptomatic at this time. While resources for children dealing with the issues associated with living in an HD family were limited to non-existent when Walt was a child, there are many resources today for children including the Huntington’s Disease Society of America (HDSA) National Youth Alliance and the Huntington’s Disease Youth Organisation (HDYO).

While this episode of Breaking Bad does contain major inaccuracies in terms of genetic testing, it does highlight the impact HD can have on children who watch their parents live with the disease.

KP 2014

 

More

Inhibition of mitochondrial protein import by mutant huntingtin

Inhibition of mitochondrial protein import by mutant huntingtin

Research has shown that mitochondrial dysfunction is associated with neuronal loss in Huntington’s disease (HD). However, it is unclear how mutant huntingtin (Htt) may cause such dysfunction. Researchers at University of Pittsburg and Washington University have discovered evidence of a direct relationship between mutant Htt and the mitochondrial protein import machinery1. This study has many implications for HD research including the development of mitochondrial protein import-based therapies.

Background^

Mitochondria are specialized subunits within a cell often referred to as the ‘energy powerhouse’ as they are responsible for conversion of nutrients into energy for the cell. Mitochondria can be found in every cell of the human body (with the exception of red blood cells) and they are also responsible for calcium homeostasis and the regulation of apoptosis (programmed cell death) 2.

Unfortunately, mitochondria may not function properly due to the obstruction of important pathways, which can compromise the energy production of the cell. When mitochondria in the brain malfunction, less energy is generated within the neuronal cells, which can lead to cell injury, and eventually cell death. Therefore, neuronal cells need healthy mitochondria to survive. There is evidence that mitochondrial dysfunction may be a critical driver of HD pathophysiology1.

The mitochondrial protein import pathway is crucial for healthy mitochondrial function since proteins are often created in the cytoplasm before traveling through several complexes to make their way to the mitochondria. To stress the importance of this pathway, mitochondria contain approximately 1,500 different proteins, yet 99% of which are encoded by the nuclear genome.

The Study^

Initially, the scientists observed that mutant Htt protein, unlike normal Htt protein, was present within brain mitochondria of HD patients. They hypothesized the existence of an interaction between mHtt and some mitochondrial proteins. The researchers conducted a series of experiments using mice models and cell lines to determine what that interaction is exactly and if that interaction negatively affects the mitochondria function.

In order to further understand how this deficiency in mitochondrial protein import is occurring, the scientists further investigated the role of Htt protein using an in vitro protein import assay with a radiolabeled precursor matrix protein (pOTC) which allows the measurement of the import activity for many mitochondrial proteins. They performed this assay in normal mitochondria in the presence of either normal (23Q) or mutant (97Q) recombinant Htt fusion proteins (shorter N-terminal Htt fragments that have been tagged to allow for purification and increased expression3) and observed that, if the Htt fragment carries a polyQ expansion, it will inhibit the uptake of preproteins into the mitochondria through direct association with the TIM23 mitochondrial protein import complex1. (The TIM23 complex assists in the movements of certain proteins across the inner mitochondrial membrane into the mitochondrial matrix.) The mutant Htt does, in fact, cause mitochondrial dysfunction by interfering with the mitochondria’s protein import function.

To understand how to prevent such dysfunction, the scientists overexpressed the TIM23 complex of the mitochondria. This resulted in more pre-proteins being able to travel through the membrane and into the mitochondria, and consequently, successfully limited the problematic cell death caused by the mutant Htt. This observation confirms that the purposeful overexpression of the TIM23 complex may actually be a key therapeutic target as cell death could be avoided despite a presence of mutant Htt.

It is important to note that there is a brain-specific reduction in the activity of protein import in neuronal mitochondria, rather than an increased sensitivity to import dysfunction, as previously hypothesized. Because of the energetic demands of synaptic transmission, synaptosomal mitochondria might be more sensitive to changes in protein import.

Finally, since HD is an age-dependent progressive neurodegenerative disease, the researchers decide to investigate how age-related insults like oxidative stress (link to definition) might compound the progression of the disease. For this experiment, mitochondrial protein import activity was observed in the presence of a sub lethal dose of hydrogen peroxide. This dosage did not impact the wild type neurons. However, it did significantly decrease import activity in the 195CAG HD neurons.

Conclusion^

These results suggest that mutant Htt inhibits mitochondrial protein import via a direct interaction with the import machinery and have important implications in respect to the development of future HD therapies. Scientists can now apply these findings to target mechanisms that prevent the mutant Htt from blocking mitochondrial protein import in an attempt to prevent or delay neuronal cell death due to mitochondrial dysfunction. Such therapeutic approach could have the potential to slow down the progression of the disease and reduce the need to focus on the more difficult task of neurogenesis and network repair.

For Further Reading^

1.Yano, Hiroko, et al. “Inhibition of mitochondrial protein import by mutant huntingtin.” Nature neuroscience (2014).

2.Wiedemann, Nils, Ann E. Frazier, and Nikolaus Pfanner. “The protein import machinery of mitochondria.” Journal of Biological Chemistry 279.15 (2004): 14473-14476.

3. “GST-tagged Proteins – Production and Purification.” GST-tagged Proteins. N.p., n.d. Web. 02 July 2014.

4. . Johri, A. & Beal, M.F. Antioxidants in Huntington’s disease. Biochem. Biophys. Acta 1822, 664–674 (2012).

K. Powers 2014

More

Emotional Recognition Deficits

It is well documented, as reviewed by Labuschagne et al. (2012), that Huntington’s disease (HD) patients often have difficulty recognizing facial cues and understanding emotions of other individuals1, especially regarding the emotion of disgust2. Such emotional deficits can greatly diminish their ability to communicate, which may result in aggravated tension and stress between patients and caregivers.

In order to understand the potential spectrum of emotional recognition deficits in HD and its relationship to certain medications, a recent study conducted as part of a multi-site international project (TRACK-HD) examined emotion recognition in relation to the use of neuroleptic and selective serotonin reuptake inhibitor (SSRI) medications1.

What are neuroleptic and SSRI medications?^

Neuroleptic drugs are anti-psychotic medications that affect one’s cognition and behavior. These drugs have the potential to cause apathy, reduced range of emotion, confusion and agitation3. Physicians prescribe HD patients neuroleptics in order to treat chorea and behavioral disturbances such as irritability and anger outbursts, and less often for psychotic symptoms1.

SSRIs are anti-depressant medications, which, on top of being used for depression treatment, may also be used to subdue behavioral issues such as irritability and aggression3.

In clinical trials focusing on diseases other than HD, these medications have been found to reduce emotional capabilities and cause symptoms such as affective indifference, emotional blunting, reduced facial expressiveness, and reduced intensity and frequency of emotional experiences1. The aim of this study was to determine if these observations are applicable to the HD patients.

Method^

The researchers identified 344 participants that ranged from premanifest patients (individuals which have already been diagnosed as carriers of the HD mutation, but have yet to start displaying any signs of HD-related symptoms ; n=115), early HD patients (n=113), and controls (n=116). The participants were between 18 and 65 years of age with no history of other neurological illnesses. Using six emotional expressions and a neutral expression, the researchers examined how these three different groups would identify and respond to the emotions demonstrated. Additionally, the researchers focused on the subset of early HD patients who were taking neuroleptic or SSRI medications in order to compare the emotion recognition performance with that of early HD patients who were not taking these medications.

In order to gage emotional recognition, the researchers utilized a computer tablet to show facial stimuli from the Ekman and Friesen face stimulus set5. Each experimental trial included a single face showing one emotional expression (anger, disgust, fear, happiness, sadness, or surprise) or a neutral expression. Subsequently, participants were advised to press one of the seven emotional word response labels displayed below the facial stimuli, allowing them ample time to signify the emotion of the face. Each participant performed 70 experimental trials.

Results^

Overall, symptomatic participants were significantly impaired when it came to recognizing the following individual emotions: anger, fear, and surprise. This impairment is greater than that observed in the unaffected controls and the premanifest groups. Those in the early stage of HD who were taking the neuroleptics were significantly less accurate at recognizing the emotions of fear, happiness and sadness than the unmedicated group. However, members of the early HD group who were taking SSRI medication had results that correlated with improved facial recognition, particularly for disgust and sadness emotions.

Implications^

This study showed that neuroleptic use by HD patients was associated with worse facial emotion recognition, whereas SSRI use was associated with better emotion recognition. These findings are of high significance for HD patient care since medications commonly prescribed to patients may difficult communication and affect social interactions. HD patients are more susceptible to misinterpret neutral events that are actually irrelevant as something that is significant, leading to issues such as depression. Prescribing medication-targeting symptoms such as depression seems to further alter the ability of those affected to communicate or read emotional cues from those around them. Therefore, a better understanding of the effects of neuroleptics and SSRIs is of great importance.

Further reading^

1. Labuschagne, Izelle, et al. “Emotional face recognition deficits and medication effects in pre-manifest through stage-II Huntington’s disease.” Psychiatry research 207.1 (2013): 118-126.

This scientific article is the primary article describing the experiment regarding emotional face recognition issues among different stages of Huntington’s disease.

2. Kipps, C. M., et al. “Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington’s disease.” Journal of cognitive neuroscience 19.7 (2007): 1206-1217.

This study by Kipps et al. focuses on some of the first research regarding emotional recognition in Huntington’s disease patients.

3. “Depression (major Depressive Disorder).” Selective Serotonin Reuptake Inhibitors (SSRIs). Mayo Clinic, n.d. Web. 02 July 2014.

The Mayo Clinic describes the use of SSRIs in the treatment of depression.

4. Cubeddu, Richard Finkel, Michelle A. Clark, Luigi X. (2009). Pharmacology (4th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 151.ISBN 9780781771559

This resource profiles the function and use of psychiatric drugs such as neuroleptics and SSRI.

5. Ekman, Paul. “Facial expressions.” Handbook of cognition and emotion 16 (1999): 301-320.

This handbook covers various tools, techniques and practices for studying cognition and emotion.

K. Powers 2014

More

Help 4 HD International Symposium 2014

On Friday, July 19, HOPESters Natty, Preston and Kristen made the trip down to Santa Maria, California to attend the first ever Help4HD International Symposium. The mission of Help4HD International is to facilitate conversations in the research community by providing vital information regarding research and clinical trials to the Huntington’s disease community.  For more information on the organization visit: www.help4hd-international.org

Below are the summaries of all the keynote speeches with attached video archives of the presentations:

Congresswoman Lois Capps, Representative, Santa Barbara County^

Congresswoman Lois Capps, the US Representative, Santa Barbara County, made the opening address at the event. She commended the Huntington’s disease community for its resilience in the face of adversity and called for the community to continue to advance on three fronts: supporting caregivers, caring for the sick and bolstering research efforts. Rep. Capps also highlighted the policy advances in assisting Huntington’s disease afflicted individuals and their family such as the HD Parity Act which aims to waive the 24-month waiting period for Medicare eligibility for Huntington’s disease patients. In addition, as a member of the Rare Diseases Caucus, Rep. Capps pledged to push for the study of rare diseases and is positive that the research on rare diseases will produce a ripple effect that will benefit patients of other illnesses like Huntington’s disease.

Dr. Ira Shoulson, Founder HSF (Huntington Study Group) and PSG (Parkinson Study Group)^

Dr. Ira Shoulson, the founder of the Huntington Study Group and Professor of Pharmacology, Neurology and Human Sciences in Georgetown University, was the first keynote speaker at the symposium. Dr. Shoulson focused on the different organizations involved in research, current state of clinical research, and explored the future of Huntington’s disease treatments. He highlights the concern of patients who register for clinical trials, as they are often worried that they might be assigned to receive the placebo treatment; he addresses this concern by emphasizing the documented benefits of the placebo effect. Furthermore, Dr. Shoulson talks about the measures put in place to protect patients undergoing clinical trials, such as informed consent measures and the regulatory processes of the FDA. He then concludes his presentation by discussing the current and future direction that Huntington’s disease research will move in. Dr. Shoulson mentions that current research can be divided into several areas: environmental factors, movement treatment, cognitive-enhancement, and gene expression modification. In the future, he believes that clinical trials may explore treating individuals possessing the dominant Huntington’s disease gene but have yet to develop the symptoms.

Ray Dorsey, MD, MBA, Professor of Neurology and Co-director, Center for Human Experimental Therapeutics ^

Dr. Ray Dorsey, who joined the symposium via a Skype Call, investigates new treatments for movement disorders. Using web-based conferencing, his work seeks to provide care to those with Parkinson’s disease and other diseases, regardless of their geographic location.

Dr. Dorsey began his talk by asking the community to consider what they could do to help the HD community advance research and what clinicians can do to relieve the burden of those affected by the disease.

He stated that the greatest accomplishment in recent medicine was the transformation of HIV/AIDS from a fatal disease to a chronic, manageable one in the past 30 years. Despite a lack of information about retroviruses and the immune system, researchers were able to develop and obtain FDA approval for an effective drug. Now, over the last generation, about ten drugs have been discovered to treat HIV. People can now live healthy, productive lives for decades.

He asks the audience if scientists can do something similar for Huntington’s disease. For example, Nancy Wexler came from a family affected by HD and was able to identify the gene that caused Huntington’s disease. This occurred at a time where genes were thought to cause these diseases, but it was unheard of to determine their location.

Dr. Dorsey then transitioned to how he is advancing the state of Huntington’s disease care through his work with the study, Connect. Huntington. Due to the lack of resources available to individuals in remote or rural regions, telemedicine has become increasingly important as a mechanism to provide these individuals with the care they need. These resources include consultations with neurologists and other doctors on various issues. Individuals should not be denied treatment due to their location.

The aim of the Connect.HD is to provide care to those affected by HD directly in the individual’s home via internet-connected devices like smartphones or computers. There are five states participating in this study, including California. Requirements include the presence of Huntington’s disease in the home as well as access to an internet-connected device. If you are interested in participating in this study, contact Ray Dorsey at ray.dorsey@ctcc.rochester.edu

Dr. Suzanne Pontow, Co-director, Umbilical Cord Blood Collection Program^

Dr. Suzanne Pontow, Co-Director of the California Umbilical Cord Blood Collection Program at the UC Davis Health System and a Stem Cell Research Program Supervisor at the Institute for Regenerative Cures, discussed both research and clinical applications, specifically for HD patients, for neonatal stem cells and the California Umbilical Cord Blood Public Bank.

She explained that a major research tool for the Institute is the use of neonatal stem cells both in research and clinical applications. The neonatal stem cells are collected from placental tissues and cord blood. The stem cells are made up of mesenchymal and hematopoietic cells, which are multipotent cells. Multipotent cells can differentiate into many but not all types of cells. For instance, hematopoietic stem cells can differentiate into several types of blood cells and mesenchymal cells can differentiate into bone cells, cartilage cells or fat cells, but they are limited to differentiation into these areas. However, both hematopoietic and mesenchymal cells can be induced into a pluripotent state from which they can become any type of cell in the human body.

Dr. Pontow described one example, in which researchers worked with a group of at-risk newborns for autism spectrum disorders. Researchers isolated hematopoietic stem cells from the cord blood of newborns at risk for Huntington’s disease shortly after birth. The cells were cultured, induced into a pluripotent state and were differentiated into neurons. By studying these neurons, they could see if the neurons were developing normally and examine how the neurons responded to various drugs as a way to look for cures or to slow progression of the disease. This “disease in a dish” model is applicable across a wide range of disease types and allows researchers to conduct extensive research about a disease without invasive patient procedures.

Neonatal cell studies are of great importance when it comes to finding treatments for disease. These cells are readily available, easy to harvest and are “youthful”, which according to Dr. Pontow, means that they “last longer in culture and go through more successful divisions than adult derived stem cells.” These advantages allow easier assessment of immune system development and function, making neonatal cells an attractive research and therapeutic tool. With the creation of The California Umbilical Cord Blood Collection Program, there should be more of these cells available for different applications.

Dr. Peg Nopoulos, Professor of Psychiatry, Neurology, UI HD, Kids HD/Kids JHD^

Dr. Peg Nopoulos, Professor of Psychiatry, Neurology and Pediatrics in the University of Iowa, focused her discussion on juvenile Huntington’s disease (JHD).  Dr. Nopoulos explained the genetics behind JHD and the differences between the symptoms of adult onset HD and juvenile onset HD. She talked about the Kids-HD program, which is a specialized program where HD experts research on reducing the length of time for diagnosis of potential patients. Dr. Nopoulos explained there are difficulties diagnosing a non-specific symptom because current diagnostic tools cannot distinguish between children with and without the disease due to behavioral cues. Instead, she recommended the use of quantitative MRI as a more accurate tool, which measures the caudate volume of the brain.

Dr. Jan Nolta, Director UC Davis Stem Cell Program, Institute for Regenerative Medicine^

Jan A. Nolta, director of the UC Davis stem cell program and the UC Davis Institute for Regenerative Cures, is moving forward with groundbreaking plans to use mesenchymal stem cells (MSCs) as delivery agents for two potential treatments for Huntington’s disease, BDNF (brain derived neurotrophic factor) and RNA interference. Her research goal is to slow down the striatal (responsible for movement control and communication) degeneration and coax new striatal neurons to be formed in HD patients. Her approach is to use MSC adult stem cells from the bone marrow to repair damaged tissues by responding to the scene of injury and producing healing factors.

A few years ago, she received a grant from the California Institute of Regenerative Medicine to prepare for a clinical trial, where they would implant into the brains of Huntington’s disease victims mesenchymal stem cells that have been engineered to secrete the BDNF needed to protect neurons and keep them healthy. She also has a separate multi-million dollar grant from the state stem cell agency to develop an RNAi delivery system using mesenchymal stem cells. If the trial of MSCs with BDNF is successful, it will provide proof of principle for MSCs as a delivery system for RNAi. “These grants are extremely important to California and to the field of regenerative medicine,” said Nolta. “They enable our teams of scientists and clinicians to plan stem cell clinical trials that will offer treatments to patients who currently have few if any other medical options.”

Patients with HD have much lower levels of BDNF than usual in their brain tissues and mutant protein blocks production of BDNF at RNA level. Nolta’s safe and effective strategy is to use mouse models to produce BDNF from MSCs transplanted into the striatum as a way to delay progression and potentially recruit new neurons. Her initial data, in conjunction with previous reports, indicate that instriatal BDNF delivery, via MSCs, can prevent motor dysfunction and neuropathological abnormalities in rodent models of HD

Mr. Kevin McCormack, Communications Director, the California Institute for Regenerative Medicine^

Mr. Kevin McCormack, Communications Director of the California Institute for Regenerative Medicine, emphasized the importance of the role of patient advocacy in making a difference for other Huntington’s disease patients and their families. Mr. McCormack explained that he and many others were working to connect patient advocates for Huntington’s disease to form a collective voice to impact policy decisions. He concluded his address by reinforcing the California Institute for Regenerative Medicine’s commitment to improve the lives of patients.

Kayla Horton, Graduate student, CIRM Bridges to Stem Cell Research^

Kayla Horton is from a family both affected by Huntington’s disease and cystic fibrosis. Her familial connections motivated her to study medicine. Horton is studying the use of human fat tissue as a source of stem cells as she is trying to discover the difference between studying adipose cells versus bone marrow in the context of stem cell research.

Mesenchymal stem cells (MSCs) have many advantages. They are easily accessible, hypo-immunogenic, anti-inflammatory, capabilities for neurogenesis and angiogenesis.

However, there are some delivery disadvantages. This study is looking for non-invasive delivery of this treatment through intravenous administration. Currently, direct implementation means brain or spinal surgery, which implants the paramedic cells.

Horton is attempting to develop a safe, non-invasive method of delivering hMSCs overexpressing neurotropic factors in order to provide neurodegenerative and protective effects to a CNS injury. Her hypothesis is to use intranasal administration of genetically modified and preconditioned hMSCs that will efficiently migrate to cell injury.

A non-invasive chemotaxic model exploits the MSCs’ innate migratory ability. They move towards the chemicals released by an injury. The goal is to deliver it through the nose, which would be non-invasive and easily repeatable as the MSCs die off.

In a recent study, the team did observe migration of cells in mice from nasal injection to the striatum, which means that Kayla Horton’s research could maybe one day provide a mechanism through which MSCs can be safely delivered to the brain without invasive surgery.

Ms. Teresa Tempkin, RNC, MSN, ANP, UC Davis HDSA Center of Excellence^

Ms. Tempkin’s primary focus is to be a part of the effort to find meaningful treatment for HD and to help families navigate their HD journey. She works with Dr. Jan Nolta and their objective is to obtain FDA approval in order to successfully complete a 2 year phase I trial of cellular therapy in patients with early stage HD. The gene therapy development candidate is donor-derived human MSCs that have been engineered to secrete brain derived neurotrophic factor (MSC/BDNF). Via recruitment from the  membership of the Huntington Study Group, her team has enrolled over 325 patients in more than 14 observational studies and clinical trials since 1997. Despite extensive knowledge of the genetics and neuropathology of HD, only palliative treatments exist.

She explained that the study has two phases: Pre-cell and HD-cell. Pre-cell study is a longitudinal observational study to enroll a cohort of early stage HD patients who are potential candidates for planned cellular therapy trial. HD cell phase is the phase 1 clinical trial of MSC/BDNF neurosurgical implanted into striatum using techniques similar to deep brain simulator implantation. In conclusion, she stated that managing expectations and burden of study for participants and caregivers is paramount and that the biggest obstacle in clinical research is time, money and FDA approval.

Dr. Ellen Feigal, Senior Vice President, Research and Development, California Institute for Regenerative Medicine^

Dr. Ellen Feigal, Senior Vice President, Research and Development, California Institute for Regenerative Medicine (CIRM), focused on the CIRM’s experience and future developments. Dr. Feigal explained the research development model used by the CIRM in managing the research projects under its charge. She also highlighted the challenges faced by research organizations in obtaining funding for conducting research.

Lavonne Goodman, MD^

Dr. Goodman began with a question: How do we reach people and get them to see the importance of clinical trials and find the energy to participate when their families are struggling with the disease? There are plenty of families that are passionate about research, but how can they garner that passion to help buoy others into participating?

It’s very hard to find treatment resources that are evidence-based. There isn’t a lot of research that has been done in this respect so the challenge for clinicians is to figure out how to manage Huntington’s disease in a way that is safe and effective.

Goodman facilitated a panel of expert physicians worldwide to figure out best practices for caring for a patient with HD. They discussed drug treatment and approached it pharmalogically, but realized the need to educate family members about the disease and teach them how to promote the health and well being of Huntington’s disease patients. One can print out the documents and take them to one’s physician in order to provide a resource of care.

Goodman studied chorea, obsessive compulsion, behavior issues and is now presently looking at psychosis, apathy, anxiety, agitation and sleep disorder. There is currently no evidence-based treatment for these symptoms. The goal is to give some guidance to patients, families, generalists on how to properly manage these specific symptoms.

For more information on the algorithm and Dr. Goodman’s work, visit http://hddrugworks.org/

Dr. Nathan Goodman, PhD, Systems for HD^

Dr. Nathan Goodman is a senior scientist at The Institute for Systems Biology in Seattle. A PhD computer scientist, he has expertise and extensive history in the building and management of large databases in biologic systems. He, with support from the Hereditary Disease Foundation, is the primary author of HDBase, a web site which assembles datasets of interest to HD researchers, including reported drug studies in HD mouse models. He is in charge of web-based data acquisition and storage. His presentation was on technology-driven research for HD treatments.  To find drugs, he stated that we should start at the start and fix the “bad gene”. The second idea is to shut down the “bad gene” via ISIS RNA drugs. The third idea is to find earliest effects via human observation trials or study of HD mice. He talked about methods to find genetic modifies to slow down HD. One method he mentioned is the ISB method, which is a whole genome sequencing of HD families and individuals.

The first ever Help4HD Symposium ended with two powerful advocate stories by Francis Saldaña and Margaret Gallardo.

KP, PL & NJ 2014

More

La enfermedad de Huntington en Sudamérica

Sudamérica es una región rica en la historia de la Enfermedad de Huntington (EH en español o HD en inglés). Dentro de este continente, la investigación ha sido muy importante y necesaria para descubrir el gen que causa la EH.  Esta investigación se puede atribuir principalmente a que la concentración más grande de las familias afectadas en el mundo vive en esa área. A pesar de la importancia que representan las poblaciones de Sudamérica para la investigación de la enfermedad, se carece de recursos suficientes para los pacientes de dicha región.

Esta sección de Global HD tiene como objetivo destacar a aquellos países en Sudamérica que tienen una historia y una significancia en relación al contexto de la Enfermedad de Huntington.

Venezuela^

La visión de conjunto^

La enfermedad Huntington (EH) es el trastorno poli nucleótido más prevalente en Sudamérica. En Venezuela, la prevalencia de la enfermedad es 1 en 20,000 personas.  Sin embargo, Maracaibo, uno de los regiones de los lagos más al norte del país, tiene una prevalencia de 7 casos entre 100 personas. Como resultado de esto, Venezuela es un país muy importante porque hay muchas personas en Maracaibo que pueden avanzar la investigación en relación a esta enfermedad.

La historia^

Americo Negrette nació en Venezuela en 1923 y estudió medicina en la Universidad Central de Venezuela. En 1942, mientras instruía en la región San Francisco de Maracaibo, Negrette se percató de pacientes caminando entre las calles con andares extraños, a quienes las personas de la localidad se refieren como “Santiveros.”  Negrette identificó así la enfermedad hereditaria de Huntington, también conocida como “el mal de San Vito.” En 1955, Negrette presentó sus observaciones clínicas al VI Congreso de las Ciencias Médicas en Venezuela. En 1963, dedicó dos secciones de su libro a la enfermedad y su expresión en sus pacientes.

Años más tarde, Nancy Wexler, una científica americana, y su equipo empezaron a colaborar con las familias afectadas de Maracaibo. Como resultado de los avances en la investigación del ADN recombinante, el “equipo de Gene Hunter,” como se les llamaba, fueron capaces de iniciar un estudio en el que se crearon las genealogías de las familias de la vasta red de los pacientes de la región.

Debido a que el registro de la genealogía fue tan completa, los investigadores fueron capaces de descubrir que todos los residentes del Lago Maracaibo tienen un antepasado común, María Concepción Soto, quien llegó en la región durante el siglo XIX  Ella es considerada la “fundadora” de aproximadamente 20,000 descendientes en riesgo de contraer la enfermedad que se pueden remontar de ella.

Con estos datos, el equipo fue capaz de reducir el lugar específico del gen de la enfermedad de Huntington en 1983. Este descubrimiento fue muy importante, no sólo para buscar una cura, sino que, además, para comprender de la herencia genética.

Los recursos^

Casa Hogar Amor y Fe^

La Casa Hogar Amor y Fe fundada en 1999 gracias a las familias de Maracaibo quienes han contribuido a los avances científicos en la investigación de la enfermedad Huntington. Como resultado de la pobreza y la falta de los recursos en el región, Casa Hogar sirve como un sistema de apoyo para las personas afectadas por la enfermedad.

Para más información sobre la casa, visita hdfoundation.org/html/venzeula_huntington

Asociación Venezolana de Huntington^

La Asociación Venezolana de Huntington tiene muchos recursos e información en relación a la enfermedad Huntington. El sitio es en español y su enfoque es sobre los tratamientos, las conexiones médicas y las clínicas para los venezolanos.

Para más información, visita avehun-venezuela.webnode.com.ve

Perú^

La visión de conjunto^

Perú tiene la segunda población más grande de pacientes con la enfermedad de Huntington  en Sudamérica. Este país cerca del océano pacifico tiene un significante potencial para la investigación epidemiológica, pero no han habido muchas inversiones en el pasado. Similar a otras regiones afectadas en Sudamérica, Perú lucha con la provisión de los recursos básicos a las personas afectados por la Enfermedad de Huntington. Mientras que han sido pocos los investigadores que han iniciado la investigación en esta región, el desarrollo se encuentra en las etapas iniciales.

La historia^

La primera familia identificada con la enfermedad fue descubierta en 1952 en la zona norte del Perú. En 1980, se identificaron los primeros casos de la EH en Cañete. Este poblado, al sur de la capital del Lima, Perú tiene una prevalencia de 45 casos  en cada 100,000 personas. Es la segunda concentración de población más grande en Sudamérica. Los científicos han descubierto que la prevalencia se debilita a medida que se va alejando de Cañete. Por lo tanto, mientras más lejos  se encuentre de Cañete, encontramos menos casos de pacientes con EH.

Investigadores relevantes^

Dr. Carlos Cosentino^

Dr. Carlos Consentino es un investigador peruano que está estudiando la región de Cañete ha investigado su prevalencia y comenzó con una pequeña cantidad de pruebas clínicas y proyectos de investigación para la enfermedad en el país entero. Mientras los recursos en el Perú son escasos para las personas con la enfermedad, el Dr. Cosentino hace su mejor esfuerzo para proporcionar servicios tales como el asesoramiento genético y el apoyo a familias con personas afectadas por la enfermedad.

Los recursos^

La sociedad Huntington de Perú^

Este sociedad no tiene un sitio, pero puede enviar las preguntas a María Begazo Viza cuyo , e-mail es mbegazo8@LatinMail.com

Chile^

La visión de conjunto^

En un país con más de 15 millones de personas, hay sólo 300 casos reportados con la enfermedad de Huntington, la mayoría se encuentran en las ciudades grandes como Santiago. La Agrupación Huntington de Chile cree que hay una prevalencia más alta, pero hay pocos esfuerzos o recursos disponibles para recopilar datos precisos dentro Chile, específicamente en las regiones rurales, en donde el 15% de la población vive. Por lo tanto, se necesita mayor análisis de datos para evaluar la población afectada por la enfermedad en Chile.

Las personas importantes^

Dr. Claudio Hetz^

Dr. Hetz, un profesor de inmunología y enfermedades infecciosas de Harvard, sirve como un co-director del Instituto de Neurociencia Biomédica de la Universidad de Chile. Con un equipo de científicos chilenos, el Dr. Hetz desarrolló un virus terapéutico que al ser examinado con ratones, se encontró ser muy efectivo en el control e incluso en la reducción de los síntomas de la EH. Este tratamiento se aplicó directamente al cerebro para revertir el daño del nervio en la región. Pese a que este tratamiento no está disponible en humanos, los resultados indican un futuro prometedor para futuras pruebas clínicas. (Si desea leer el artículo científico completo se puede acceder aquí).

Rodrigo Osorio^

Rodrigo Osorio es un emprendedor chileno, presidente de la Fundación Chilena de Huntington y fundador de la Red Latinoamericana de Huntington, un recurso, este sitio está en Español que proporciona información sobre la enfermedad, con recursos específicos de las regiones de Latinoamérica. Con el apoyo de Osorio, fue posible la construcción del primer Centro Diurno para enfermos con Huntington que viven en Santiago. Con el apoyo de los proyectos como Factor-H (Ver: Los Recursos en Sudamérica), Osorio y sus organizaciones varias tratan de proporcionar más recursos básicos para mejorar la calidad de vida para las personas afectadas por la enfermedad de Huntington en Latinoamérica.

Los recursos^

La mayoría de chilenos viven en las ciudades (85%), de los cuales un 40% de los habitantes urbanos viven en la capital, Santiago.  Muchas familias con la enfermedad, que han sido identificadas viven en esta región. Para apoyar a estas familias, Rodrigo Osorio recientemente creó el Centro Diurno Huntington para los pacientes afectados por la enfermedad, construyendo esto con el apoyo de muchas organizaciones de Huntington como CETRAM, la Agrupación Chilena y dos organizaciones gubernamentales. Después de cinco meses en ejecución, la calidad de vida de los pacientes que asistieron al centro mejoraron cerca de un 32% (en general, como la medida del índice de la calidad de vida). (Para ver la presentación de Rodrigo al Congreso Mundial de la enfermedad Huntington en 2013,  haga clic aquí). Sin embargo, muchas regiones en Chile carecen de este tipo de recursos básicos para las familias, específicamente fuera de las áreas urbanas. Sin embargo, es complejo ayudar o acceder a estas poblaciones porque no han sido bien identificados o localizadas en Chile. Por lo tanto, se debe desarrollar un trabajo más exhaustivo en esta área para así poder asignar los recursos que correspondan.

Agrupación Chilena de Huntington ^

Esta organización tiene como objetivo el suministrar información de calidad sobre los tratamientos psicológicos, medicamentos y tratamientos  y la mejora de prácticas así como el prestar del red de apoyo para los chilenos afectados por esta enfermedad.

Instituto de Biomédica y Neurociencia ^

Aplicando una estrategia integrada y multidisciplinaria el BNI tiene por objetivos: (i) explorar la organización estructural y funcional del cerebro en condiciones normales y patológicas, tanto a nivel de organismos completos como a nivel celular, (ii) capacitar y organizar a una nueva generación de investigadores y clínicos en un entorno transdisciplinario único, (iii) producir investigación clínica de alto nivel y transferir sus resultados a la sociedad mediante el descubrimiento de nuevos enfoques diagnósticos y terapéuticos para mejorar la calidad de vida de los pacientes neurológicos o con trastornos psiquiátricos, y (iv) convertirse en un centro de recursos para profesionales clínicos especializados y el público en general.

Lectura complementaria^

“Chile.” Wikipedia. Wikimedia Foundation, n.d. Web. 18 Jan. 2014. <http://en.wikipedia.org/wiki/Chile>.

“Estudio: Cómo Es Vivir Con Huntington.” LaSegunda.com. N.p., 16 Mar. 2012. Web. 20 Jan. 2014. <http://www.lasegunda.com/Noticias/Buena-Vida/2012/03/730292/Estudio-Como-es-vivir-con-Huntington>.

Brasil^

La visión de conjunto^

Como resultado de un país de tan grande extensión como Brasil, no hay números definitivos en relación a la prevalencia de la enfermedad en el país. Sin embargo, hay regiones específicas donde la enfermedad de Huntington ha sido localizada en el sector de Feira Grande en el norte de Brasil. Los investigadores identificaron 22 casos de HD adentro de la población de 22,000 este país. Este número indica una prevalencia de 1 entre 1000 individuos que desarrollará la EH. La prevalencia de EH es resultado del alto número de matrimonios entre hermanos en esta región.

La historia^

No hay un gran registro sobre la historia de Brasil respecto a la enfermedad de Huntington. Las normas culturales y sociales dentro de este país han sido enfáticas a la hora de mantener el secreto dentro de las familias cuando se refiere a la EH. Debido a este estigma, los científicos sólo han comenzado a estudiar las poblaciones como un resultado del lento proceso de desmantelamiento de dicho estigma.

Los investigadores, sin embargo, ahora han determinado – tentativamente- el origen de la enfermedad en Brasil. Muchas de las genealogías muestran rastros de África, dado que muchos brasileros tienen ancestros de negros africanos que fueron forzados a venirse a Sudamérica durante el periodo de esclavitud. Sin embargo, sí parece haber una leve variación dentro de estas poblaciones, especialmente debido a la mezcla entre familias. Ahora bien, pese a que la forma genética de la enfermedad existe aquí in Brasil y pareciera que fueron los descendientes africanos quienes trajeron consigo un fenotipo similar a la EH (HDL). Se requiere de mayor investigación para lograr determinar la prevalencia y la historia de la EH en Brasil.

En Septiembre del 2013, Brasil organizó el congreso mundial de la enfermedad Huntington. Este congreso fue un hito importante para los brasileros afectados, debido principalmente  al estigma que rodea la enfermedad que ha obstaculizado el desarrollo social en la región por décadas. Sin embargo, los anfitriones del congreso destacaron constantemente su emoción al llevar a cabo el congreso en Brasil como una etapa importante en vías de la eliminación del estigma social.

Las personas importantes^

Dr. Monica Santoro Haddad^

Dr. Haddad, director de la Academia Brasileña de Neurología, ha estado apoyando activamente las familias afectadas durante 25 años de su carrera. Ha trabajado con más de 400 familias en el Hospital das Clínicas de la Universidad Sao Paulo  y tratando a un menor porcentaje de éstas en su práctica privada (Serbin, 2013).

En una entrevista que se llevó a cabo para Serbin, Dr. Haddad explica como la discriminación en Brasil ha generado grandes obstáculos para ayudar a las personas afectadas por la EH. Como ya mencionamos anteriormente, el estigma tiene un gran peso en lo que previene a las personas afectadas por la enfermedad a hablar de ésta con personas que no son parte de sus familias. Ahora, si una persona afectada no muestra síntomas o si no han confirmado su estatus genético con un examen, ignoran su existencia. Esta repuesta afecta a la población entera con EH en Brasil porque sólo hay un grupo pequeño de personas que están dispuestas a participar en los estudios clínicos, que puede ayudar a conducir a tratamientos y finalmente, una cura para la enfermedad. También, y a diferencia de lo que sucede en los E.E.U.U., los brasileños no participan activamente por la causa ni donan dinero a las organizaciones sin lucro, causando una gran escasez en el financiamiento.

El Dr. Haddad espera que el Congreso mundial 2013, que se celebró en Rio de Janeiro, promueva la idea de la participación al interior de la comunidad Brasileña afectada así como que aumenten los números de participación para las pruebas clínicas, específicamente ENROLL-HD.

Los recursos^

Asociación Brasileña de Huntington ^

La misión de esta Asociación es la de proporcionar apoyo directo a las familias afectadas, así como educar a los profesionales sobre las peculiaridades de la enfermedad que deben tomarse en consideración.

Lectura complementaria^

Alencar, Lopez, Figueiredo, and Monileó. “Prevalence of Huntington’s Disease in Feira Grande, a Small City in Northeastern Brazil.” Journal of Neurology, Neurosurgery, and Psychiatry (2010): 81. Print.

Burton, Adrian. “Hope, Humanity, and Huntington’s Disease in Latin America.” The Lancet Neurology12.2 (2013): 133-34. Print.

Serbin, Ken. “At Risk for Huntington’s Disease.” : Brazil’s Big Place on the Huntington’s Disease Map. Cure HD, 2 Apr. 2013. Web. 19 Jan. 2014. <http://curehd.blogspot.com/2013/04/brazils-big-place-on-huntingtons.html>.

Teive, Hélio. “Huntington’s Disease like Phenotype: New Date from Brazil and What We Knew between Heaven and Earth.” Arquivos De Neuro-Psiquiatria 69.3 (2011): 417-18. Web.

Colombia^

La visión de conjunto^

Colombia no refleja la prevalencia astronómica de la enfermedad como es el caso de su país vecino, Venezuela. Sin embargo, hay varias comunidades claves donde se han experimentando los efectos devastadores de la enfermedad: Magdalena, Juan de Acosta, Antioquía, Chocó, Medellín y Bogotá. Estas regiones difieren de muchas otras regiones en el mundo, debido a que los afectados a menudo viven en extrema pobreza, que no sólo afecta el bienestar del paciente, sino que a esto se suma la tensión financiera, física y emocionalmente, para los miembros de las familias y los cuidadores. Así, una de las principales problemáticas de las familias en estas regiones es la falta de los recursos básicos.

El significado cultural^

La escasez de los recursos básicos se torna en un gran problema para las personas que viven con la enfermedad en Colombia. Muchas de las familias viven en extrema pobreza y con malas condiciones de vida. Estas condiciones pueden afectar la calidad de vida, tales como la escasez de alimentos, de agua potable y la dificultad de acceso y salida de sus viviendas.

Factor-H es un organización que busca mejorar la calidad de vida de los pacientes enfocándose principalmente en regiones como Medellín, una gran cuidad urbana en la parte central de Colombia. Medellín se caracteriza por sus vastas redes de tugurios y viviendas de bajos ingresos. Debido a la presión financiera  sobre las familias de Huntington, la mayoría de aquellos que experimentan los síntomas motores a menudo terminan en barrios marginales. Estas condiciones habitacionales pueden ser muy peligrosas para aquellos con estas condiciones motores, por ejemplo, la extensa cantidad de callejones, niveles y escaleras que una persona necesita atravesar para hacer su propio camino.

Las familias con la EH en Colombia, así como en otros países similares en América del Sur, enfrentan diversos retos diferentes a los de las familias en otros países del mundo dada las condiciones de extrema pobreza. Si esto dificulta la capacidad para proporcionar la ayuda necesaria para una familia promedio, mucho menos en aquellas familias con varias personas que presentan síntomas de la EH. Por lo tanto, se hace imperativo destacar la importancia de los sistemas de soporte estructural que son necesarios para una adecuada atención médica en este país.

Los recursos^

Fundación Huntington de Colombia^

Esta fundación busca mejorar la calidad de vida para las familias con Huntington en Colombia. Este blog sirve como un recurso para la comunidad.

Asociación Colombianos por la Enfermedad de Huntington^

Esta asociación sirve como un recurso primario para las familias e individuos afectados para la enfermedad en Colombia.

Lectura complementaria^

1. Factor-H (factor-h.org)

Un proyecto social sin ánimo de lucro que persigue aumentar la conciencia sobre las personas que conviven con la enfermedad de Huntington o están afectadas por la misma, así como facilitar ayuda humanitaria y médica para disminuir el sufrimiento de las comunidades locales en América Latina.

2. Moscovich, Mariana, Renato P. Munhoz, Nilson Becker, Egberto Reis Barbosa, Alberto J. Espay, Roberto Weiser, and Hélio A.G. Teive. “Américo Negrette and Huntington’s Disease.” Arquivos De Neuro-Psiquiatria 69.4 (2011): 711-13. Print.

Una entrada de diario que relata la obra de Américo Negrette, una figure hisórica importante en la investgacion de la enfermedad Huntingon.

3. Red Latinoamerica de Huntington (rlah.net)

Un grupo de profesionales de la salud, científicos y familiares que aportamos a la investigación en búsqueda de tratamientos efectivos para la Enfermedad de Huntington

Muchas gracias a los editores por su ayuda: María Jesús Osorio Lafontaine y Erica Fernandez Zamora

Si tiene algunas recomendaciones, visita nuestra página de contacto aquí.

K. Powers 2014

More

Google Glass and HD

The part of the brain most affected by Huntington’s disease, the basal ganglia, are groups of nerve cells (neurons) at the base of the brain. Basal ganglia are responsible for the motor movements of the muscles in the body. When cells in basal ganglia die, a common pathological symptom of HD, a person experiences uncontrollable muscular movements similar to that of fidgetiness. Another disease that produces similar uncontrollable movements symptom is the Parkinson’s disease due to the disease’s effects on a specific area of the basal ganglia called the substantia nigra.

A new app for intelligent glasses, such as Google Glass, might make it possible to improve the gait of patients suffering from Parkinson’s disease.

More

HD in Australia

Australia is a part of world where extensive research regarding Huntington’s Disease has been done on a variety of different subtopics. Researchers have been able to draw conclusions about reproduction, age of onset, and the origins of the disease. They have also come to realize that prevalence varies throughout the continent, reaching as high as 12.1 individuals per every 100,000 in some areas. In an attempt to support individuals affected by HD, Australia appears to have developed a large and supportive HD community spread throughout the continent. In fact, the 2011 World Congress on Huntington’s Disease was hosted in Melbourne, Australia.

This section of Global HD aims to highlight regions within Australia in which the HD populations have been studied, and where history and significance within the HD context have been demonstrated.

Tasmania

An Overview^

Tasmania, an island state located 150 miles off the southern coast of Australia, is the region within the Australian Commonwealth that has been shown to have the highest prevalence of HD, with 12.1 cases per 100,000 people. This is a unique and somewhat surprising finding considering that, in most Western countries, it is predicted that the prevalence of HD is 5 to 7 cases per 100,000 individuals, which is a statistic that is more on par with the rest of the Australian continent. The unusually high prevalence that has been noted in Tasmania has prompted researchers to conduct a variety of studies regarding the region’s HD population, making it a well-studied and important area in the context of global HD.

History^

In 1949, Dr. Charles Brothers came across a large Tasmanian family that was presenting symptoms of HD. This family has continued to be studied over the years, but for medical confidentiality purposes, they are known in research literature only as “the Brothers family.”

It is believed that HD was first brought to Tasmania in 1842 by an English woman identified as “Mary.” Mary was born in Long Sutton, Somerset, England in 1806, and appears to have inherited the disease from her father, “Robert,” who was born in 1776 in Somerset. Researchers have named “Robert” the originator of HD in Tasmania, and he is considered to be the first generation of the Brothers family.

Mary married several times before leaving England for Launceston, Tasmania with her husband, “Charles,” and her seven children in 1842. Mary proceeded to give birth to seven more children in Tasmania. Of her 14 children, nine developed HD. All nine children later went on to have children of their own. As of 1990, seven of these nine lineages still had living descendants, with six branches containing descendants that were either at risk or affected by HD.

Nine generations of the Brothers family have been studied, and more than a century after Mary’s death, there have been 765 identified family members living at risk. The average age of onset for affected Brothers family members was found to be 48.6 years old, and the average age of death was 61.8 years. Fertility studies showed that there was no evidence that suggests that the ability to reproduce was negatively impacted in any of the affected individuals. In fact, the disease appeared to correlate with greater fertility amongst Brothers family members, while led to past (and now out-dated) medical recommendations that at risk individuals be sterilized once they had achieved their desired family size.

Studying the Brothers family lineage provided researchers with a better understanding of HD and helped explain the higher than expected prevalence of HD in Tasmania by allowing them to trace the disease back to a single common ancestor.

The fact that Tasmanians with HD can be traced back to a common ancestor appears to explain the higher than expected prevalence of HD in Tasmania.

The Global HD research and articles received partial support from the Bingham Fund for Innovation in the Program in Human Biology.

Resources in Tasmania^

Huntington’s Disease Association within the Tasmanian Department of Health and Human Services

The Huntington’s Disease Association provides support for Tasmanians affected by HD. The Association supports Tasmanian people of any age, including those living with HD, families of those affected, caregivers, and anyone at-risk of developing HD. The association can provide financial and moral support, special equipment, food supplements, information booklets, and introductions to others affected by HD.

For more information regarding the association, please visit: dhhs.tas.gov/au/service_information/service_files/huntingtons_disease_association

Australian Huntington’s Disease Association Tasmania Inc.

The Association was established to develop educational programs and provide support for Tasmanians affected by HD. It aims to assist families with coping with and understanding the disease, all while helping these families develop a strong unified voice.

For more information regarding the association, please visit: huntingtonsaustralia.asn.au

R. Reddy 2014

More

World Congress 2013 – Coping Skills Session

In September 2013, several HOPES student researchers attended the Huntington’s Disease World Congress, held in Rio de Janeiro, Brazil. Summaries of the all the sessions attended can be found in the Conferences and Conventions section of our site.

The HOPES trip to the 2013 World Congress received partial support from the Bingham Fund for Innovation in the Program in Human Biology.

Coping Skills Session

One of the most difficult ideas to accept about Huntington’s Disease is that (currently) there is no cure or treatment: it is fatal and devastating. Given this harsh reality, some of the most important skills for patients and their loved ones to acquire involve those associated with coping. On the second day of the HD World Congress in Rio de Janeiro, three lecturers shared their research and personal experiences about how to cope in a world with HD.

Suicidality in Huntington’s Disease^

The first lecture entitled “Suicidality in Huntington’s Disease” was given by the researcher Aam Hubers from the Netherlands. Hubers explained that HD patients are between two and eight times more likely to commit suicide, amount to 5.7% of HD deaths coming from suicide. Five to ten percent of HD patients attempt to commit suicide, and on average at least 11% of patients admit to having had suicidal ideation within the most recent month. Suicidal ideation occurs most when patients begin having possible symptoms of HD, meaning that 20% of newly premotor symptomatic patients and newly motor symptomatic begin having suicidal ideation. These patients are more likely to use antidepressants, have a depressed mood, and tend to be more aggressive and anxious. Given these disturbing statistics, Hubers explained how her future research was aimed at discovering how HD patients who experienced suicidal ideation coped and resisted making a suicide attempt. Her data collection revealed the pressing necessity for a deeper exploration of how HD specifically can cause psychological problems and how those problems can be addressed with and without medication.

Gene Veritas^

The second lecture, “Gene Veritas”, was presented by Kenneth Serbin from the United States. Serbin explained that his mother and himself had both tested positive for the HD gene, and after her death he began to search for ways to cope with what seemed like a death sentence. Serbin mentioned twelve of the coping strategies that he had written about on his blog so far at cureHD.blogspot.com. These included:

-Learning about the disease

-Gaining discipline from exercise

-Having a healthy diet

-Studying available supplements (creatine, CoQ, Omega 3, blueberry concentrate, etc)

-Taking psychiatric medications, as they have been show to have a neuroprotective effect

-Going to support groups and psychotherapy

-Meditating

-Finding a passion in life

-Doing “neurobics” (mental aerobics) to increase BDNF in the brain

-Going public about having HD to overcome denial and stigma

– Becoming an advocate to connect with people

-Assisting with research studies

Serbin uses these coping skills and more, he explained, to be proactive in his own health and the HD community. With the current state of scientific research, Serbin genuinely believes that testing positive for HD is no longer a death sentence if one takes control of their HD diagnosis now.

Living with HD^

The third and final lecture in this session was entitled “Living with HD – Then and Now” and was given by Charles Sabine from the United Kingdom. Structured mostly as a motivational presentation, Sabine told his story about HD in his family. His father was diagnosed with HD in 1984, and surrounding that diagnosis were fear, shame, and ignorance. In 2005, Sabine and his brother both tested positive for the gene, but Sabine used his own diagnosis as a platform to emphasize the power of patient organizations in the HD community. He utilized his position as a public figure to support the passage of the Genetic Information Nondiscrimination Act (GINA) in 2008 in the United States, which protects Americans from discrimination against employers and insurance companies based on genetic information, and gave media coverage in Britain of HD organizations, events, and bills, which he continues to do today. Sabine closed his lecture noting that testing positive for HD in the present is a much less negative experience than in the past specifically because of amazing outreach done by patients and their families.

These three lectures shared one common, inspiring theme: though there is not currently a cure for HD, there is still hope! Whether it is hope for a treatment, for personal longevity of life, or even just hope for support from the HD community, there are always ways to maintain a positive outlook on living with HD if one manages to realize the exciting possibilities the future holds for curing this disease.

C. Bartlett 2013

More

HD in South America

Para un versión en Español, haga clic aquí

South America is a region rich with the history of Huntington’s disease. Within this continent, important and necessary research for the discovery of the HD gene has taken place. This research can be attributed to the fact that the largest concentration of families in the world affected by HD lives here. Despite the importance of South American populations to HD research, resources for HD patients in this region are few and far between.

This section of Global HD aims to highlight countries in South America that have history and significance within the HD context.

Please stay tuned as we update this site with more country-specific information.

The Global HD research and articles received partial support from the Bingham Fund for Innovation in the Program in Human Biology.

Venezuela^

An Overview^

Huntington’s disease is the most prevalent polynucleotide disorder in South America. In Venezuela, the overall prevalence of HD is 1 in 20,000 people. However, Maracaibo, one of the most northern lake regions in the country, has a prevalence of 7 cases per 100 people. As a result, Venezuela is an extremely important country in the context of global HD.

History^

Americo Negrette was born in Venezuela in 1923 and studied medicine at the Central University of Venezuela. In 1942, while instructing in the San Francisco region of Maracaibo, Negrette noticed patients walking throughout the streets with strange gaits, referred to by the local people as “Sanviteros.” The hereditary disease, which Negrette accurately identified as HD, was called “el mal de San Vito” (the illness of San Vito). In 1955, Negrette presented his clinical observations at the Sixth Medical Sciences Congress in Venezuela. In 1963, he devoted two sections of his book to HD and its expression in his patients.

Years later, after the death of Dr. Negrette, a student trained under his direction published information on cases of HD in the Maracaibo region. Negrette’s student had unknowingly located the population that would lead to many discoveries concerning the genetic origins of HD.

In 1979, Nancy Wexler, an American scientist, and her team began a collaboration with the affected families of Maracaibo. Due to breakthroughs in recombinant DNA research, the “Gene Hunter team”, as they were called, were able to initiate a study in which they created pedigrees, or family trees, of the vast network of HD patients in the region. Because the genealogy record was so thorough, the researchers were able to discover that all the residents of Lake Maracaibo had a common ancestor, Maria Concepcion Soto, who first arrived in the region sometime in the 19th century. She is considered the “founder” since approximately 20,000 descendants at risk for HD could be traced back to her.

With this wealth of data, the team was able to narrow down the location of the HD gene in 1983. This discovery was a huge scientific breakthrough, not only in the search for a HD cure, but also for understanding genetic inheritance.

Resources^

Casa Hogar Amor y Fe (House of Love and Hope)

Casa Hogar Amore y Fe, The House of Love and Hope, was created in 1999 as a thank you to the families of Maracaibo who had contributed to the scientific advancements in HD research. Due to the immense poverty and lack of resource in the area, Casa Hogar serves as a support system for those suffering from Huntington’s disease.

Asociacion Venezolana de Huntington

The Venezuelan Association for Huntington’s offers resources and information relating to Huntington’s disease. The website is in Spanish and focuses on treatments, medical connections, and clinics available to Venezuelans.

Peru^

Overview^

Peru contains the second largest population of HD patients in South America. This country bordering the Pacific Ocean contains significant potential for epidemiology research, but so little has been invested in it to date. Similarly to other affected regions within South America, Peru still struggles with providing basic resources to those affected by Huntington’s disease. While some researchers have initiated research in the region, progress is still its beginning stages.

History^

The first family identified with Huntington’s disease was discovered in 1952 in the northern region of Peru. In 1980, the first cases of HD were identified in Cañete. This region, south of the capital of Peru, Lima, has a prevalence of 45 cases per 100,000 individuals. It is the second largest concentration of Huntington’s disease in Latin America. Scientists have discovered that the prevalence weakens the further the distance from Cañete, meaning the further one travels from Cañete, the smaller the population of HD patients becomes.

Important Researchers^

Dr. Carlos Cosentino

Dr. Carlos Cosentino is a Peruvian researcher studying the region of Cañete. He has researched its prevalence, as well as created some of the first clinical trials and research projects for the disease in the entire country. While resources in Peru are vastly underfunded for those with Huntington’s disease, Dr. Cosentino is doing his best to provide services such as genetic counseling and family support to those affected.

Resources^

Huntington Society of Peru

This society does not have a website, but inquiries can be sent to Maria Begazo Viza. To contact her, e-mail mbegazo8@LatinMail.com

Chile^

Overview^

In a country of over 15 million people, there are currently only 300 reported cases of Huntington’s disease, many of them recorded in major cities such as Santiago. The Chilean Huntington Society believes there to be a higher prevalence, but there have been few efforts or resources available to collect accurate data within Chile, especially in the rural regions, in which 15% of the population resides. Further data analysis is necessary in order to assess the population affected by Huntington’s disease in Chile.

Important Figures^

Dr. Claudio Hetz

Dr. Hetz, adjunct professor of immunology and infectious disease at Harvard, serves as co-director of the Instituto de Neurociencia Biomédica de la Universidad de Chile. With a team of scientists in Chile, Dr. Hetz developed a therapeutic virus that, when tested with mice, was found to be highly effective in controlling, even reducing, symptoms of HD. This treatment was applied directly to the brain, reversing nerve damage within the region. While this treatment is not available to humans, the results do indicate promise for future clinical trials (The full scientific article can be accessed here.)

Rodrigo Osorio

Rodrigo Osorio is a Chilean businessman who serves as the president of the Fundación Chilena de Huntington. Osorio founded Red Latinoamericana de Huntington, an online resource in Spanish that provides information about Huntington’s disease, with resources specific to regions of Latin America. With Osorio’s support, the first day center for Huntington’s disease patients was built last year for those living in Santiago. With the support of projects like Factor-H (see Resources in South America), Osorio and his various organizations seek to provide more basic resources to improve the quality of life for those affected by Huntington’s disease in Latin America.

Resources^

The majority of Chileans reside in cities (85%), with 40% of urban dwellers living in the capital city, Santiago. Many Huntington’s disease families, that have been identified, reside in this region. In order to support these families, Rodrigo Osorio, the president of the Fundación Chilena de Huntington, recently created a day care center (El Centro Diurno Huntington) for Huntington’s disease patients, built with the support of several Huntington’s disease organizations such as CETRAM, the Agrupacion Chilena de Huntington, and two governmental organizations. After five months in operation, the quality of life for patients who attended the center improved by about 32% overall (as measured on a quality of life index). (To view Odrigo’s presentation at the 2013 World Congress on Huntington’s Disease, click here.) Many regions in Chile lack these type of basic resources for HD families, especially outside urban areas. However, it is often difficult to help these populations because they have not been thoroughly identified or located in Chile. More work in this area must be done in order to allocate resources accordingly.

Agrupacion Chilena de Huntington

This organization has multiple objectives that include providing quality information on psychological treatment, drugs, best care practices, as well as a support network of Chileans affected by this disease.

Biomedical Neuroscience Institute

BNI brings together basic and clinical neuroscientists to 1) explore the structural and functional organization of the brain, 2)produce high-level clinical research, discover new diagnostic and therapeutic approves to improve quality of life for patients with neurological/psychiatric disorders, 3) train a new generation of researchers, and 4)serve as a resource center for specialized medical professionals and the general public. (This description is a rough translation of the website description from Spanish to English)

Further Reading^

“Chile.” Wikipedia. Wikimedia Foundation, n.d. Web. 18 Jan. 2014. <http://en.wikipedia.org/wiki/Chile>.

“Estudio: Cómo Es Vivir Con Huntington.” LaSegunda.com. N.p., 16 Mar. 2012. Web. 20 Jan. 2014. <http://www.lasegunda.com/Noticias/Buena-Vida/2012/03/730292/Estudio-Como-es-vivir-con-Huntington>.

Brazil^

Overview^

Due to the size of a country like Brazil, there are no definite figures of prevalence across the entire country. However, there are specific regions where Huntington’s disease has been located such as Feira Grande in Northern Brazil. Researchers identified 22 cases of HD within the population of 22,000 here. This statistic indicates a prevalence of 1 in 1,000 individuals will develop HD. This rate is due to the high amount of sibling marriages in the region.

History^

There is very little recorded history in Brazil in respect to Huntington’s disease. The social and cultural norms within this country have emphasized secrecy when it comes to families affected by disease. Because of this stigma, scientists have only recently begun studying HD populations due to the slow process of dismantling this stigma.

Researchers, however, now have tentatively determined the origin of the disease in Brazil. Many of the genealogies show traces to Africa, as many Brazilians have Black African ancestors that were forced to South America during the slave trade. However, there does appear to be some variation within these populations, especially as families have interbred. While the genetic form of Huntington’s disease does exist here in Brazil,  it appears that African descendants brought with them a Huntington’s disease-like phenotype (HDL). More research is needed to determine the prevalence and history of HD in Brazil.

In September 2013, Brazil hosted the World Congress on Huntington’s disease. This Congress was a significant milestone for Brazilians affected by HD, as the stigma surrounding the disease has hindered social progress here for decades. The disease is often kept a secret by family members; there are no exact estimates on the population count for those affected by HD in Brazil. However, the hosts of the Congress frequently emphasized their excitement of having the Congress in Brazil, as it is a major first step in removing the social stigma.

Important Persons/Researchers^

Dr. Monica Santoro Haddad

Dr. Haddad, director of the Brazilian Academy of Neurology, has actively been supporting Huntington’s disease families during her 25-year career. She has worked with over 400 families at her clinic in the Hospital das Clínicas of the University of Sao Paulo and has even treated some of these families through her private practice (Serbin, 2013).

In an interview conducted by Ken Serbin, Dr. Haddad explains how discrimination in Brazil has created major obstacles in respect to aiding those affected by HD.  The stigma carries great weight and prevents people from talking about it with non-family members. Currently, if people affected by the disease do not show symptoms or have not confirmed their genetic status with the test, they often ignore its existence. This response affects the entire HD population in Brazil because very few people are willing to participate in clinical studies, which could help lead to treatments, or ultimately, a cure. Additionally, unlike Americans, Brazilians do not often participate in causes or donate their money to non-profit organizations, causing a major shortage in funding.

Dr. Haddad hopes that the 2013 World Congress, which was held in Rio de Janeiro, promotes the idea of active participation within the Brazilian HD community, as well as increases participation numbers for clinical trials, especially Enroll-HD.

Resources^

Asosocioa Brasil Huntington

The mission of the association is to provide support and guidance to families affected by the disease, as well as educates professionals about the peculiarities of the disease that should be taken into consideration.

For Further Reading^

Alencar, Lopez, Figueiredo, and Monileó. “Prevalence of Huntington’s Disease in Feira Grande, a Small City in Northeastern Brazil.” Journal of Neurology, Neurosurgery, and Psychiatry (2010): 81. Print.

Burton, Adrian. “Hope, Humanity, and Huntington’s Disease in Latin America.” The Lancet Neurology 12.2 (2013): 133-34. Print.

Serbin, Ken. “At Risk for Huntington’s Disease.” : Brazil’s Big Place on the Huntington’s Disease Map. Cure HD, 2 Apr. 2013. Web. 19 Jan. 2014. <http://curehd.blogspot.com/2013/04/brazils-big-place-on-huntingtons.html>.

Teive, Hélio. “Huntington’s Disease like Phenotype: New Date from Brazil and What We Knew between Heaven and Earth.” Arquivos De Neuro-Psiquiatria 69.3 (2011): 417-18. Web.

Columbia^

Overview^

Columbia, the neighbor of Venezuela, does not reflect the astronomical prevalence of Huntington’s disease, as in Venezuela. However, there are several key communities experiencing the devastating effects of the disease: Magdalena, Juan de Acosta, Antioquía, Chocó, Medellín, and Bogotá. These regions differ from many other HD regions worldwide, as those affected often live in extreme poverty, which not only affects the well-being of the HD patient, but also adds to the financial, physical, and emotional strain of the family members and caregivers. One of the greatest issues with HD families in these regions is the lack of basic resources.

Cultural Significance^

A lack of everyday resources is often a huge issues for those living with Huntington’s disease in Columbia. Many of these families live in extreme poverty with poorly suited living conditions. These conditions can affect quality of life as food is often scarce, water may not be suitable for drinking, and moving in and out of the home might be impossible.

Factor-H, an organization working to enhance quality of life for this living with HD in South America, is focusing on regions such as Medellín, a large urban dwelling in the central part of Columbia. Medellín is infamous for its vast network of slums and low-income dwellings. Due to financial strain on Huntington’s disease families, many of these individuals experiencing motor symptoms end up in slums. These living conditions can be extremely dangerous for those with motor symptoms as there are often many levels of stairs and alleyways one must navigate in order to make his or her way.

Families with HD in Columbia, and other similar South American countries, face different challenges than families in other countries as they are often dealing with overwhelming poverty. This makes it difficult to provide for an average family, let alone one with multiple people exhibiting signs of HD. Columbia is important in that it highlights the structural support systems required for proper medical care in this region.

Resources^

Fundacion Huntington de Columbia

This foundation aims to improve the quality of life for those suffering with Huntington’s disease in Columbia. The blog serves as a resource guide and community.

Asociación Colombianos por la Enfermedad de Huntington

The Association serves as a primary resource for families and individuals affected by the disease in Columbia.

Additional Resources in South America^

1. Factor-H (factor-h.org)

A not-for-profit social project to increase awareness about people living with and affected by Huntington’s disease, and to facilitate humanitarian and medical aid to diminish the suffering of local communities in Latin America.

2. Moscovich, Mariana, Renato P. Munhoz, Nilson Becker, Egberto Reis Barbosa, Alberto J. Espay, Roberto Weiser, and Hélio A.G. Teive. “Américo Negrette and Huntington’s Disease.” Arquivos De Neuro-Psiquiatria 69.4 (2011): 711-13. Print.

A journal entry chronicling the work of Américo Negrette, an important historical figure in Huntington’s disease research.

3. Red Latinoamerica de Huntington (rlah.net)

Un grupo de profesionales de la salud, científicos y familiares que aportamos a la investigación en búsqueda de tratamientos efectivos para la Enfermedad de Huntington.

K. Powers 2014

More

Trojan Therapy

The blood-brain barrier (BBB) is a layer of cells that block most molecules from entering the brain in order to protect this sensitive organ from external invaders. It does its job so well that delivering treatments to the brain is extremely difficult and poses a great challenge to drug development.

BBB

 

BBB2

Researchers from the University of Nebraska Medical Center, the University of North Carolina, and Lomonosov Moscow State University in Russia have found a potential solution. In early 2013, these collaborators announced that they were successful in delivering an enzyme to the site of cell death within the brain of a mouse experiencing poor motor function characteristic of Parkinson’s disease.  The researchers accomplished targeted delivery through a method called Trojan therapy. This article will explain the concept of Trojan therapy, as well as its potential application for Huntington’s disease.

What is Trojan Therapy?^

The method for drug delivery is named for the Trojan War tale, during which one army snuck past the defenses of their enemy by disguising themselves within large wooden horses. The horse was presented as a gift and when it was brought behind the city’s defenses the army used the element of surprise to defeat the enemy forces.

Trojan therapy works in a similar fashion. The blood-brain barrier serves as a fortress wall for the brain. In this case, researchers disguised potential treatments within macrophages, immune cells that are allowed entry past the blood-brain barrier, making it possible to deliver the targeted therapy straight to the cells that need it.

The scientists utilized an antioxidant enzyme (proteins that combat oxidative free radicals within the body) known as catalase, to prevent cell death within the mouse brain affected by Parkinson’s disease. They engineered macrophages to carry the genetic material for catalase past the blood-brain barrier and into the brain. Once inside the brain, the macrophages attached to dying neurons, stimulating signals that called for backup to repair these neurons.

The Science behind Trojan Therapy^

Oxidative stress can lead to cell damage by producing free radicals, highly reactive molecules that can indiscriminately react with and damage cellular components. Reducing excess free radicals with antioxidants is an attractive possible method to reducing inflammation caused by cell damage in Parkinson’s brains. In the past, introducing antioxidant therapies has proven unsuccessful because the treatments were not able to overcome the blood-brain barrier.

In order for this type of therapy to function properly, blood-borne macrophages must be able to carry antioxidant proteins across the blood-brain barrier to affected areas of the brain. In this study, the scientists loaded the macrophages with nanozymes, a type of enzyme that was used to clear out free radicals from the brain.

BBB3

Once the macrophage finds its way into the brain, there are three options for the nanozyme to reach its specific target in the brain:

1) Transient fusion of cellular membranes

2) Formation of macrophage bridges (physical structures that repair cellular gaps) and cellular movement mechanisms and,

3) Release of exosomes – large vesicles or storage pockets in the cell – containing the nanozyme. 1

Exosomes appear to be most promising for targeting cell death as research has shown they are excellent long-distance cellular transporters. They effectively transport many biological molecules involved in making proteins from the information contained in genetic material, including proteins, mRNA, and microRNA (Zomer et al, 2010). Researchers engineered macrophages to release exosomes containing DNA, mRNA, transcription factors (proteins that attach to DNA and control transcription of genetic information to messenger RNA) and an encoded catalase protein to assist in reducing inflammation of the brain. In Parkinson’s disease mouse models, the researchers discovered that sustained production of catalase resulted in inflammatory and neuroprotective outcomes, meaning cell death and brain atrophy was not as likely in those mouse models treated by the macrophage Trojan therapy.

The expression of the encoded catalase included within the macrophage increased over time, while DNA levels remained constant, which has implications for the therapeutic efficacy. An antioxidant with greater positive outcomes might be able to be transferred to needy neurons through this mechanism of delivery.

Conclusion of Findings^

The control group for this experiment utilized mouse models without inflammation.  The experimental group included mice exhibiting motor signs of PD. After injecting the PD mice with the macrophages, noticeable changes occurred. The fluorescent markers used to tag the progress of the materials packaged within the macrophage showed thorough coverage of the brain, especially to regions of inflammation where cell repair support was needed. These mice were able to perform just as well as the control mice on balance tests after receiving the Trojan therapy.

Oxidative stress can lead to cell damage. Reducing excess free radicals is an attractive method of reducing inflammation in PD brains. In the past, these methods have proven unsuccessful due a lack of mechanisms to deliver therapeutic drugs across the blood-brain barrier. The research conducted by this collaboration of scientists is the first to find a potential route for overcoming these obstacles. In fact, this method might be more effective than traditional viral vector gene therapy used for these purposes.

The research by the University of North Carolina and Lomonosov Moscow State University highlights various issues faced by clinical researchers. As outlined in this article, ability to cross the blood-brain barrier plays a major role in therapy design. Additionally, as the brain is a very sensitive organ, it is difficult to gauge the toxicity thresholds for various treatments and medications. Exosomes, unfortunately, are not a silver bullet either. The efficiency of loading drugs into exosomes is a challenge, as well as the difficulty in targeting the exosome to a particular cell type or organ.

Scientist Andrew Feigin of Hofstra North Shore-LIJ School of Medicine is currently leading a human-based clinical trial in which he is trying to use virus-delivered gene therapy for PD. This method has more sustained impacts than macrophages, but is much harder to get through the brain as the immune system fights these foreign viruses trying to pass the blood-brain barrier.

Researcher Elena Batrakova of University of North Carolina aims to deliver growth factors into the brain utilizing macrophages, in order to stimulate the growth of neurons. She believes that macrophages are the solution to reversing neuronal death in patients with PD. To-date this research has only been conducted in mouse models. In order to start human trials, scientists need to prove the safety of this therapy, as well as assure this therapy can be repeated successfully. This process could take several more years before human trials begin.

What does this research means for HD?^

While this study focuses on Parkinson’s disease, overcoming the challenge of effectively delivering medicine across the blood-brain barrier could be useful in preventing damage or repairing brain cells in any of the neurodegenerative disorders, including Huntington’s disease. If HD scientists develop drugs or treatments that could slow down or reverse neuronal death in Huntington’s disease patients, macrophage-based delivery, as pioneered in this research, could be a method for getting that medication across the blood brain barrier and into regions of the brain where the medication is needed. If a method of drug delivery, such as Trojan therapy, could be proven safe, effective, and broadly applicable, it would allow scientists to concentrate on drug development.

For Further Reading

1. Haney, M. J., Zhao, Y., Harrison, E. B., Mahajan, V., Ahmed, S., He, Z., … & Batrakova, E. V. (2013). Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases. PloS one, 8(4), e61852.
2. Ahmed, Abdul-Kareem. “A Trojan Treatment for Parkinson’s Disease.” MIT Technology Review. MIT, 14 Oct. 2013. Web. 04 Nov. 2013.
3. Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, et al. (2010) Exosomes: Fit to deliver small RNA. Commun Integr Biol 3: 447–450.


KP 12/6/13 More

Companion Animals and Health

When most people consider therapies, they often think of prescriptions and side effects. However, animal companion therapy is proving to be an effective means of improving well-being among patients. Many of the benefits of animal companion therapy can extend to patients and family members living with Huntington’s disease. This article highlights the physical effects caused by companion animals, as well as opportunities for taking advantage of this type of therapy.

The Physical Effect of Companion Animals^

Stress can have harmful effects on the body’s ability to cope with various health issues. Research consistently shows that exercise and meditation can help manage stress levels. More recently, the scientific community has begun to collect growing evidence that animal companions might have the same effect on the health of patients.

The presence of an animal alone can affect our emotions. Animals are often able to focus people’s attention in a way that is calming or de-arousing (Cirulli et al., p. 342). Since animals, especially dogs, respond with affection and generally pro-social behaviors, they can potentially serve as an “emotional bridge” within therapeutic contexts.

The physical health effects of a companion pet can range from everyday benefits to life-saving changes. Within the first few months of acquiring a pet, patients tend to have lowered risk for cardiovascular disease, increased chances of surviving myocardial infarctions, decreased need of physician services during stressful life events and a reduction in everyday minor health problems.

Many HD patients cite lack of familial support as a major problem. Companion animals could help mediate this gap as icebreakers, bridging people with the outside world and jumpstarting communication and social exchanges that can promote feelings of social integration. Research in nonhuman mammals suggests that oxytocin, a signaling molecule in the brain, helps to increase one’s feeling of reward during social interactions while also increasing bonding between individuals. Oxytocin also assists in responding to social stress for humans. In fact, interacting with a dog caused a significant increase in levels of oxytocin within the human, improving his or her ability to forge new social bonds.

Creating an animal companion relationship^

In the study, Animal-assisted Interventions as Innovative Tools for Mental Health, researchers state that dogs are the ideal animal companions. Over thousands of years of domestication, dogs have been “selected for characteristics that enhance their sensitivity to a wide range of human communicative signals, both visual and acoustic” (Cirulli, p. 341). Dogs develop complex communication systems with humans and are highly interactive. Additionally, dogs provide opportunities for physical, recreational, and social activities. They are easily trained to constructively work in different settings, which explain their use as Seeing Eye and rescue dogs.

HD patients who live in nursing homes are often under great duress, as institutionalization can result in a decreased quality of life and stress due to separation from loved ones. Dog-mediated interventions could improve communication and reduce loneliness and depression.

Furthermore, animal companions could also help children of families experiencing traumatic life occurrences. Animal companions have been shown to influence social, emotional, and cognitive development in children. Parents often report that an animal helps teach children about life events. Children who grow up with pets have an enhanced sense of empathy and responsibility, social status within the peer group, and higher self-esteem and self-confidence.

While the positive aspects of animal companionship seem numerous, there are studies that raise questions about the extent of this impact. Visiting dog programs do not consistently “improve mood, cognitive abilities or social interactions” (Cirulli, p. 344). This might indicate that perhaps longer-term, matched interaction is needed between animal and human to see any effects. In fact, saliva spits revealed that there is a time-dependent increase in behavioral results such as improvement in mood or social bonding, as measured by mood changes and cortisol levels. (Cortisol is a hormone often associated with stress. Long term interaction with animals has shown to decrease levels of this hormone, improving well-being.)

Adding Pets to the Home^

In summary, adopting a companion animal into a Huntington’s disease family or an institution housing HD patients might have marked effects on the well being of various participants. However, there are certain aspects to take into account when making the decision to add a family member to the home. To find more information about the logistics of adopting a pet, visit http://www.aspca.org/adopt/adoption-tips.

If you are concerned with integrating a pet into family experiencing health difficulties, please contact Pet Partners, an organization dedicated to “improving lives through positive human-animal interaction.” Visit their website at http://www.petpartners.org/.

For Further Reading:^

1. Cirulli, Francesca, Marta Borgi, Alessandra Berry, Nadia Francia, and Enrico Alleva. “Animal-assisted Interventions as Innovative Tools for Mental Health.” N.p., n.d. Web. 14 Oct. 2013.
2. Bekoff, Marc, Ph.D. “Pets Are Good for Us: Where Science and Common Sense Meet.”Psychology Today. N.p., 23 July 2010. Web. 14 Oct. 2013
3. Allen, Karen M., Jim Blascovich, Joe Tomaka, and Robert M. Kelsey. “Presence of Human Friends and Pet Dogs as Moderators of Autonomic Responses to Stress in Women.” Journal of Personality and Social Psychology 61.4 (1991): 582-89. Print.
4. Health Benefits of Animals. Pet Partners, n.d. Web. 14 Oct. 2013. .

K. Powers
10/31/2013

More

HDSA 20th Anniversary of Gene Discovery Symposium

The Huntington’s Disease Society of America hosted the “20th Anniversary of HD Gene Discovery: Lessons Learned” celebration symposium in the Hart Senate Building in Washington D.C. on Wednesday, April 3, 2013. HOPES was able to send a representative to the event. This is a summary of the representative’s experiences.

 

The Huntington’s Disease Society of America (HDSA) hosted an educational, free symposium to celebrate the discoveries and accomplishments made in the twenty years since Nancy Wexler and teams of “gene hunters” discovered the location of the gene that causes Huntington’s disease (HD) on chromosome 4 (More on the huntingtin gene here). A panel of speakers – all former members of the gene hunter teams – spoke about the past, present, and future of HD research.

Dr. Francis Collins, MD, PhD, Director of the National Institutes of Health (NIH)^

 

The day started off with a presentation by Dr. Francis Collins, director of the National Institutes of Health (NIH). While at the University of Michigan, Dr. Collins was an instrumental member of one of the teams invested in finding the location of the HD gene.

Dr. Collins declared the month of April to be one of many celebrations. Sixty years ago, in 1953, the paper describing the structure of the double helix in DNA was published. Thirty years ago, in 1983, scientists successfully mapped chromosome 4. (Mapping means the scientists were successfully able to determine the location of the genes on that chromosome.)Twenty years ago, the location of the HD gene on chromosome 4 was discovered. Finally, only ten years ago, under the direction and leadership of Dr. Collins as director of the NIH, the human genome was finally sequenced.

The NIH is a part of the U.S. Department of Health and Human Services and is the “nation’s medical research agency making important discoveries that improve health and save lives” (NIH.gov). The NIH is the largest supporter of biomedical research in the world. Their goals for improving the lives of millions are ambitious, but necessary. Dr. Collins stated that the NIH is working on re-engineering the drug discovery pipeline while removing bottlenecks in the process. The National Health Service formed the National Center for Advancing Translational Sciences (NCATS) whose work is to advance projects that will remove bottlenecks in the drug discovery process, such as a chip that screens for the toxicity of certain drugs using induced pluripotent stem cells. The chip will assist in determining whether or not a drug will pass the blood-brain barrier prior to beginning clinical trials. The NIH is also a major funder of various areas of Huntington’s disease research, such as mitochondrial DNA maintenance, huntingtin protein biology, translational therapeutics, and Sirt 1/BDNF metabolism.

The BRAIN Initiative, recently announced by President Obama, will invest $100 million into mapping the systems of the brain beginning in fiscal year 2014. Essentially, mapping means scientists will have a better understanding of how and why the brain is connected. This will theoretically help researchers develop better treatments and cures based off of this information.

Tracing Our Roots: Nancy Wexler, PhD^

 

Dr. Nancy Wexler is an iconic figure in the world of HD research. After watching her mother suffer from the disease, Nancy’s entire family invested their lives into the search for a cure. Nancy Wexler’s father met with Marjorie Guthrie, Woody Guthrie’s widow, and decided to create the Hereditary Disease Foundation. The mission of the Hereditary Disease Foundation, at the time, was to seek out and create collaborations amongst the world’s brightest scientists dedicated to curing HD. There were many complex challenges. At the time, it was believed that humans didn’t have biological markers, or indicators of a biological state that highlights certain genetic abnormalities, which would make it nearly impossible to discover what was causing genetic disease. However this did not stop the scientists.

Dr. Wexler first ventured to Venezuela in July of 1979. Venezuela contains one of the largest HD families in the entire world. Wexler and her team made the treacherous journey to Lake Maracaibo where they studied over 18,000 people. After collecting blood samples and family lineages, Dr. Wexler discovered that HD was first brought to this region by a woman in the 1800’s, potentially a slave or mistress of a European.

With a combination of the information collected from this Venezuelan family, as well as that of the American family that Dr. Collin’s lab studied, many new developments followed. The Venezuelan information led to the discovery that the CAG repeat length corresponds to age of onset of disease symptoms and indicated that environmental and other genetic factors can affect the age of onset. The combination of research findings led the scientists to chromosome 4, and more specifically, the mutation responsible for HD in 1993.

Dr. Wexler described not only her scientific efforts, but her humanitarian ones as well. The Venezuelan family members affected by HD were extremely poor. Many lived in huts and slept on dirt floors. There was no Western medical care whatsoever. When Dr. Wexler returned to the United States, the Hereditary Disease Foundation donated funds to create Casa Hogar, a home for families affected by the disease. Since 1979, the Hereditary Disease Foundation has donated over $17 million to bettering the quality of life of Venezuelans afflicted by this disease.

Dr. Nancy Wexler finished her talk by stating her belief that the cure lies in tackling the disease progression via the silencing of the mutant gene.

 

Current Affairs: James F. Gusella, PhD^

Dr. Jim Gusella was another gene hunter who was instrumental in finding the location of the gene. He concentrated his talk on various HD basics.  With the discovery of the HD mutation in 1993, scientists were able to determine the genetic difference between a normal person and HD person at any age. While we may take this achievement for granted twenty years later, at the time the development was a huge boost to understanding the underpinnings of HD. The “trigger of this entire process of genetics is now known.”

Huntington’s disease affects compounds that control the manifestation of the disease. Symptoms can be determined before genetic diagnosis as specialized doctors now have enough information to understand the cognitive, psychological, and physical features of the disease.

Dr. Gusella finished his talk with the same message as Dr. Wexler. He said that it is best to think of this disease as a process that must be stopped before any damage is done. Preventing disease progression before it starts is a guiding mission of his research group.

 

The Promise of the Future: Marcy MacDonald, PhD^

 

The last gene hunter to speak was Dr. Marcy MacDonald. Dr. MacDonald began her talk with what was becoming the theme of the symposium: Interventions must be made during, but ultimately before, a life-long disease progression.

The “big goal” of researchers is to discover a way to cut or reduce the number of CAG repeats to a normal count (individuals with 35 repeats or higher will almost assuredly have symptoms of HD in a normal lifespan). Every human being needs the huntingtin protein to function, so reducing the total levels of the huntingtin protein is likely to be detrimental. We each have two copies of the HD gene (just like all of the other genes in our bodies). For most HD patients, one copy produces a version – or allele – of huntingtin that has a normal CAG length, while the other produces the mutant version of the protein with the expanded CAG region. It is crucial to control the mutant expression and not touch the normal huntingtin protein.

Dr. MacDonald advocates that scientific research needs to shift to discovering the earliest features of disease progression, as current methods primarily analyze only symptomatic individuals. Understanding how the earliest effects of the HD mutation differ or concur in various HD populations would allow scientists to make great strides in targeting the mutant protein expression.

HD is systemic. The brain is the most important organ affected, but many more types of cells throughout the body are impacted as well. This concept has been confirmed by a study of induced pluripotent stem cells (iPS) in HD patients. This study allowed scientists to use multiple lines of iPS cells (which function similar to embryonic stem cells) to re-create and study various cell types. Dr. MacDonald stressed the need to move away from research approaches aimed at a single target in the brain, as these methods have been ineffective and cost a large amount of money. Instead, it is important to discover various cell networks and functions affected in patients at the earliest age possible and research how environmental factors can affect disease progression.

Dr. MacDonald ended by discussing how HD is a “pioneering vanguard disease.” The research produced in the last 20 years has changed the way other neurological disease and therapeutic approaches are viewed by the scientific community. Emphasizing the need to find cures not just for HD, but all neurological illnesses, creates a collaborative paradigm that allows for a successful exchange of information and research.

Question & Answer^

The day finished with a question and answer session in which attendees could inquire about certain points the scientists had made during their talk. Many of the people in the audience were personally affected by HD, whether they were caregivers, loved ones, or living with the disease. One of the overarching questions involved the fear that scientists are only realizing how much more complex this disease is, making it even harder to find the cure. Many of the attendees wondered if this meant discoveries were further down the road than previously thought. All of the scientists responded with the idea that “complexity is an opportunity” (Gusella). The more complexity, the “more possibility for solutions” (MacDonald). What was stressed to the audience, especially by Dr. Wexler, was the idea that the silencing of the mutant gene and early intervention along with potential therapies are the greatest opportunities we have for a cure.

KP

5/6/13

More

Advocacy: How to Get Involved

This article describes current advocacy efforts, including the Huntington’s Disease Parity Act, Compassionate Allowance List, and how these two types of documents affect the average Huntington’s disease family.

Advocacy, by definition, is the means through which an individual or group attempts to influence public policy. The Huntington’s Disease Society of America website states that advocacy, pertaining to Huntington’s disease (HD), is sharing your personal HD story, as well as asking elected officials to support efforts to “improve access to treatment, medical care and to find a cure.”

Huntington’s Disease Parity Act^

The Huntington’s Disease Parity Act would require the Social Security Administration to revise the disability criteria for those with HD, especially in terms of the language used to approve applicants for benefits. It would also waive the 24-month waiting period for Medicare eligibility for individuals disabled by HD. (To view the actual text of the bill, click here).

Many individuals experiencing symptoms due to HD are unemployed due to their disabilities. Because of this, they often rely on Social Security Disability Insurance (SSDI). SSDI is based upon the amount of income an individual was receiving when he/she became disabled. Payments often range from $500 to $2,000 a month. However, after qualifying for this insurance, the individuals must wait at least two years before receiving any benefits from the Medicare program. This policy is extremely problematic as many HD patients are under the age baseline for Medicare (65 years old), and yet deteriorate very quickly if symptoms aren’t addressed with proper medical care immediately after diagnosis.

The HD Parity Act would correct this problem by waiving the 24-month waiting period as it did for patients with amyotrophic lateral sclerosis (ALS) in 2000.  (This bill passed as an attachment to an appropriations bill after confirming an influential number of co-sponsors in the House and Senate.) In addition, the SSDI guidelines for HD are almost 30 years out of date, affecting who is approved for the insurance. These guidelines do not recognize the psychological effects of HD, which can appear 10 to 15 years before motor symptoms begin. In the SSDI guidelines, HD is only defined as Huntingtons Chorea, the uncontrollable writhing movements that characterize the motor disability of HD. Correcting the medical definition would make HD patients eligible for SSDI earlier and alleviate a lot of financial hardship. According to estimates by Strategic Health Care, this bill would only cost $10-13 million a year, which is a negligible cost for Social Security Disability payments.

Efforts are being made to promote the bill and ensure that it is approved. The bill has been introduced four times previously, and is on its fifth introduction in 2015. The bill was introduced into the Senate by Senator Kirsten Gillibrand in April 2015, and currently has 1 cosponsor. In this 114th Congress, this year, it has been introduced into the House of Representatives by Representative Adam Kinzinger with 103 original cosponsors (the highest starting point yet). Additional representatives, both Democratic and Republican, have signed on as regular cosponsors, bringing the tally up to 129. This level of support is important, because it makes the bill a higher priority. Since it is starting out at a stronger place earlier in the congressional session, it is easier for legislators to find opportunities to attach it to a larger piece of legislation that is on its way to get passed. Since its inception, the Huntington’s Disease Society of America has been encouraging its support by senators and representatives and has set a goal of obtaining 175 co-sponsors.  However, this goal is flexible as it is ideal to have a majority of Congress support this initiative.  The more senators and representatives in support of this bill, the more likely it will be passed when voted upon.

To check whether or not your elected officials have supported this act, click here.

Compassionate Allowance List Update^

SSA Announces Official Inclusion of Adult-Onset HD to Compassionate Allowance List

On Thursday, December 6, 2012, the Social Security Administration (SSA) announced that adult-onset HD would be added to the Compassionate Allowance List (CAL), along with Juvenile-Onset HD, which was added in April 2012.

The CAL allows those affected by diseases on the roster to enter a fast track for applying to Social Security benefits. This means families affected by HD will no longer face rejection and postponed benefits due to outdated definitions of HD symptoms.  According to the Huntington’s Disease Society of America, the addition to the CAL “also recognizes the cognitive and psychological symptoms of HD and establishes criteria for their use in the qualification process.”

While inclusion on the CAL is a great step forward, there is still a need for the SSA to update their outdated description of HD, which defines the disease as a movement disorder (especially since the CAL language refers back to the SSA definition). CAL will not address issues of insurance. It also does not affect the language used by the SSA which does not include the cognitive and psychiatric aspects of HD, arguably the more debilitating aspects of the disease and the first to appear. These issues, along with the 2-year waiting period for Medicare eligibility, are addressed in the proposed Huntington’s Disease Parity Act, which is currently in need of more co-sponsors in both the House and Senate.

If you are interested in advocating for the HD Parity Act, visit http://www.hdsa.org/living-with-huntingtons/advocacy/ to write your senators and representatives, urging them to co-sponsor this important bill. Constituent involvement is important to elevate the importance that legislators place on the bill. Congress runs on stories from constituents; it is vital to put a narrative and a face behind the issue.

In addition, if you or someone you know affected by HD is denied disability, please contact Jane Kogan of the Huntington’s Disease Society of America. You can e-mail her at jkogan@hdsa.org for support and advice on re-applying.

The Fast Facts: A Summary^

The Parity Act Fact Sheet is a quick guide to the basic facts concerning the Huntington’s Disease Parity Act. All of these facts were compiled by the Huntington’s Disease Society of America.

1. Huntington’s disease is the only disease that is neurological, genetic, fatal disease, and rare, yet strikes during one’s working years. It is also the only disease to potentially have total cognitive, motor, and behavioral impairment, all at the same time.

2. The Compassionate Allowance Act eases the wait time for disability insurance review. However, only the Huntington’s Disease Parity Act will update the language, allowing more people with the disease to qualify for disability benefits. That means less people will be denied disability coverage.

3. The Social Security Administration (SSA) has the power to change their definition of HD. Their neurological disability guidelines expired on July 1, 2012. SSA extended their own deadline to publish the new guidelines for an additional two years. Legislation would mandate they speed up the process.

4. The HD Parity Act has an expected $260 million cost over 10 years (starting after the removal of the two-year waiting period). These estimates are based upon the costs incurred by a similar act passed for ALS (amyotrophic lateral sclerosis) in 2000. The cost of removing the two-year waiting period for all diseases is estimated to be around $113 billion over 10 years (2008 Congressional Budget Office).

5. If this legislation were passed, Medicaid savings could potentially lower the total cost of this policy by as much as 20 percent, for a total annual cost of $21 million annually (Strategic Health Care). (Strategic Health Care, a lobbyist group for the HDSA, obtained these numbers from the independent research conducted by Mathematica Policy Research and the Congressional Budget Office.)

6. The support of 218 representatives from the House and 60 senators from the Senate is needed in order to pass a bill. (The Senate number would mean there would be no possibility for a filibuster (an attempt to block  a vote for legislation through methods such as speaking for extended periods of time). In addition, there do not need to be 60 official co-sponsors, but rather 60 Senators who have shown some level of support for the bill.)

7. Members of Congress do not need to sit on the committee of jurisdiction to co-sponsor legislation. Any member of Congress has the power to cosponsor a bill, no matter what committee they serve on.

8. Amyotrophic Lateral Sclerosis (ALS) and End Stage Renal Disease (ESRD) have both received waivers for the two-year Medicare waiting period through Congressional legislation.

Anyone can be an advocate for measures that would improve the lives of those affected by Huntington’s disease. Whether it be sending your representative an e-mail urging them to co-sponsor legislation or fighting discrimination in the workplace, everyone can make a difference.

 

Further Reading^

1. “Bill Text 114th Congress (2015-2016)S.968.IS.” Bill Text of the Huntington’s Disease Parity Act. Kirsten Gillibrand, n.d. Web. 29 April. 2015.

 

This is the text of the bill introduced to Congress. View it in its entirety by clicking here.

 

2. “Advocacy.” Www.hdsa.org. N.p., n.d. Web. 11 Dec. 2012.

 

This is the Huntington’s Disease Society of America’s official Advocacy website.

3. “SSA Announces Official Inclusion of Adult-Onset HD to Compassionate Allowance List.” Message to Kristen A. Powers. 7 Dec. 2012. E-mail.

 

This is an e-mail sent out by the Huntington’s Disease Society of America. To view the web version, click here.

KP 02/15/2013 LV 04/29/2015

More

Huntington Study Group’s Huntington’s Disease Clinical Research Symposium 2012

Saturday, November 10, 2012, marked the sixth annual Huntington’s Disease Clinical Research Symposium in Seattle, Washington. This event, organized by the Huntington Study Group, was open to the public and provided an opportunity for attendees to learn about the latest in clinical research and trials.

Below are several keynote summaries and their findings:

Ashwini Rao (Columbia University) on the Role of occupational and physical therapy in improving function in Huntington’s disease^

 

Dr. Ashwini Rao of Columbia University began his presentation by outlining the definition of occupational and physical therapy. Occupational therapists are professionals who aim to improve the health of clients in their daily activities through engagement in their occupation. Health care professionals who aim to promote movement, pain reduction, and health in their clients, on the other hand, conduct physical therapy.  After overviewing the development of clinical guidelines for the therapies, Dr. Rao explained that there is an underutilization of physical therapy at all stages of Huntington’s disease (HD), particularly in the early stages.

There are several problem clusters that arise in HD patients: balance and gait, posture and balance, and hand control. The following cluster symptoms were determined from a study conducted by Dr. Rao’s lab that examined gait and balance performance. In the pre-manifest stage of HD, symptoms may be observable as slower speed, shorter stride, more variable steps, and diminished hand function. In the manifest stage, symptoms are apparent as decreased speed, shorter and more variable steps, decreased step frequency, variable timing, and difficulty with eating, writing, and household or work-related tasks. For more information on the study, please click here.

In addition to identifying problem clusters, Dr. Rao also introduced an intervention framework. He recommended that patients diagnosed with HD engage in fall prevention exercises, gait and balance training, and appropriate regular physical exercise, regardless of their stage of symptoms. Dr. Rao noted that a study published by the New England Journal of Medicine showed that 48 regular sessions of tai chi, as well as tango lessons, improved postural balance in patients with Parkinson’s disease. (For more information on this study, click here) This exercise regimen may translate to HD patients as well, with a larger number of sessions being more effective.

Dr. Rao recommended that all HD patients begin an interdisciplinary model of care, with therapy tailored to their specific stage of the disease. Dr. Rao believes that those who have been recently diagnosed and are in early stages should seek out a therapist as soon as possible. In his opinion, developing a relationship with this therapist would allow an early assessment of motor markers and the creation of an exercise program that includes strength, balance, and cardiovascular capacity components. It is extremely important to make exercising habitual, as well as involve family and close ones in a daily regimen.

As patients progress into middle disease stages, they should continue with their exercise programs, as well as transition to therapeutic exercises in order to discover markers that might indicate risks. A home assessment should be conducted to determine the need for shower chairs, safety bars, scatter rugs, and any other items that might make the home friendlier and safer. Patients should also consider assistive devices such as a walker. Dr. Rao stated, “similar to cars, four wheel drive is the best” as it improves speed, stride length, and reduces variability in motion. Footwear should contain a supportive light cushioned sole, as well as flexible upper foot and heel support.

In terms of postural control during eating, patients should consider a sturdy chair with a high back. They should also throw out all the traditional mealtime rules such as having one’s elbows on the table (a necessary strategy). It is important to remove distractions during mealtime as well.

As for financial concerns, Dr. Rao mentioned a New York Times article on the topic of a recent settlement clarifying Medicare will pay for services needed to maintain a patient’s current condition in order to prevent or slow deterioration. This includes the necessary therapies outlined in Dr. Rao’s talk.

To learn more about Dr. Rao’s research, click here.

Dr. Steve Hersch (Mass General Hospital) on the Secondary Prevention of Huntington’s disease ^

Dr. Steve Hersch of Massachusetts General Hospital described the necessity of devising clinical trial designs that include at-risk individuals that do not want to undergo genetic testing. By allowing at-risk individuals to participate without learning their CAG count, researchers can enable greater participation while preventing coercion of unwanted genetic testing. Candidates would be anonymously tested for pre-manifest HD via cognitive and blood markers, as well as neuroimaging. (For more information on neuroimaging, click here.)

Dr. Hersch then transitioned into describing the research his lab has been conducting on the safety, tolerability, and potential efficacy signals for high-dose creatine to treat HD. (For more on creatine, click here). Creatine increases brain energy and has shown to be safe and tolerable. Creatine additionally slows brain atrophy and is actually modifying the effects of HD in patients that are pre-symptomatic. However, it is not yet clear if it can delay the onset of symptoms.

In addition, Dr. Hersch stressed that the creatine used in these studies is medical grade and not the creatine often found in health stores. One should not test high doses of creatine unless done so under medical supervision. As for clinical trials, Phase III of the CREST-E study will be a more rigorous study of the efficacy of creatine. Recruitment for the trial is ongoing. (For more on the CREST-E study, click here)

Dr. Blair Leavitt (University of British Columbia) on the Changing demographics at its prevalence on HD^

Dr. Blair Leavitt of the Centre for Molecular Medicine and Therapeutics (University of British Columbia) began his presentation by describing the prevalence of HD: 5 in 100,000 globally have the disease. In British Columbia, the location of his research, HD affects at least 1 in 1000. However, there has recently been a rise in the prevalence of the disease. Dr. Leavitt mentioned that new mutations have been occurring in families where HD had previously been absent.

As life expectancy increases in the United States, Dr. Leavitt believes that HD will soon become a disease of older people as life expectancy increases, similar to how Alzheimer’s is known today. Currently, many people might have HD, but will not live long enough to express symptoms. However, as technology and medicine improves, more individuals are expected to live long enough to the point where they are symptomatic.

Lavonne Goodman M.D. on Clinical Trials: Why Isn’t Everyone Doing It?

Dr. Lavonne Goodman, HD patient advocate, cited informal surveys conducted recently aimed at understanding why more people aren’t participating in clinical trials (For more on clinical trials, click here). Their findings suggested that a lack of awareness has prevented many people from participating. Often, there is a desire to participate, but many of those affected by HD are not aware of when or where trials are happening, and why these clinical trials are being conducted. Participation rates in clinical trials increased locally when trial advocates visited HD support groups and informed the group of local trials. In addition, advocates provided information packets about these trials, and addressed members’ questions and concerns. Many of the members of these support groups asked the following questions:  What studies and trials are currently ongoing? What is available in my geographic area? Are any open for enrollment? Why are these studies being done? What is the enrollment process?

Many other barriers must be overcome to increase HD clinical trial participation. These barriers include a fear of drug risks and side effects and stress. The stress of dealing with HD is often hard enough; adding a clinical trial to one’s to-do list can seem too overwhelming. The logistics are also difficult, as one must consider time lost at work, travel expenses, and potential loss of income. And again, lack of knowledge can be a deterrent as people might not want to participate if they think they are getting the placebo, or have to stop taking drugs that currently work for them. In addition, people are afraid that confidentiality will be breached and discrimination will ensue from medical providers or insurance.

Currently, hdtrials.org and clinicaltrials.gov are two resources where individuals can learn about trials occurring in their areas. However, these two websites are not always up-to-date. The Huntington’s Disease Society of America is working on improving information about clinical trials on their website in the next few months.

KP 12/17/2012

More