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UC Davis Center of Excellence

HOPES team members Adam Hepworth and Amy Frohnmayer visited the UC Davis Center of Excellence team on August 2, 2007. The visit took place at the Veteran Affairs (VA) Hospital in Rancho Cordova, a facility which the Center uses for running clinical trials. During the visit the HOPES members had the opportunity to see exactly what takes place during a clinical visit for a participant enrolled in the COHORT trial. HOPES would like to offer thanks to all of the clinic staff who made the visit a positive experience with a special thank you to Teresa Tempkin for offering so much of her time and expertise.

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Left to Right: Amy Frohnmayer, Teresa Tempkin, Adam Hepworth

Introduction^

Although the UC Davis Center of Excellence (COE) main office is located at the Davis Medical Center in Sacramento, our visit took place at the VA Hospital in Rancho Cordova. On the fourth floor of the main hospital building, an entire wing is devoted to clinical trials run by UC Davis doctors. The UC Davis COE had reserved space on this wing to run the COHORT clinical trial.

Tempkin explained that access to these clinical research facilities was crucial for successfully running clinical trials. At the VA Hospital, she has access to space and equipment unavailable at the Davis Medical Center. Without these resources, it would not be possible for the UC Davis COE to participate in clinical trials like COHORT.

COHORT is an acronym for Cooperative Huntington’s Observational Research Trial. It is currently the largest Huntington Study Group HD clinical trial and it takes place at 40 sites in North America and Australia. It is a long term observational study with no official end date. The goal of the study is to collect a huge database of information from subjects diagnosed with HD and make that information available to researchers around the world. To that end, trial enrollees commit to annual study visits for as long as they are willing and able. The study’s control group consists of adults who are part of an HD family. This particular study does not enroll individuals who are at risk of HD but do not know their gene status. The UC Davis COE entered the trial in January of 2007 and has already enrolled over 30 participants. For more information about COHORT click here.

Behind the Scenes of a COHORT Visit^

During our visit, we were fortunate enough to observe first hand most of what happens during an annual COHORT visit. In addition to a standard physical exam, the participant undergoes a few short cognitive and neurological assessments. A variety of questionnaires are also administered to the participant. These help assess the participant’s emotional and behavioral status and help to gauge the affect of disease progression on daily living and basic skills. The participant gives a detailed medical history and reports on any medications he or she currently takes. And finally, the visit includes a blood draw. With participant consent, the blood samples collected in COHORT are placed in a research facility and made available to HD researchers around the world. This is one unique aspect of the study that offers an amazing opportunity for HD researchers. Because all of the information collected during a participant’s annual visit is matched by code (all personal identification information is kept strictly confidential) to his or her blood sample, researchers using the samples can also have the benefit of knowing a huge variety of information about the status and progression of HD in the individual to whom the sample belongs. This additional body of information linked to every blood sample allows for much more sophisticated research and analysis.

Some of the procedures during the visit are fairly generic and could easily take place in any clinical research trial, while others are tailored specifically to HD participants. For instance, one of the cognitive tests administered was a short mental exam. One part of this test includes questions designed to measure a subject’s orientation in time and space, ability to maintain focus and attention, and basic communication skills. Although these are all important cognitive abilities, they are not usually the functions impaired by HD, which tends to negatively affect executive function. A later cognitive test looked specifically at executive function through tests of concentration and multitasking ability. That test tends to be more sensitive to cognitive changes in an HD patient.

The neurological examinations also include both more general tests and specific tests best suited for an HD population. Although it is common to think of chorea as the definitive neurological sign of HD, the COHORT neurological exam looks for many other HD-specific symptoms. Tempkin explained that although chorea is one of the most visually dramatic signs of HD, it is not usually the most debilitating aspect of the disease. Problems with balance and fine motor coordination are more likely to lead to serious complications through injuries like falls. Chorea is also extremely variable, and progresses at a different rate in different patients. This makes it especially important to test a variety of motor changes. The COHORT exam includes tests for characteristically abnormal eye movements, motor impersistence, speech changes, muscle stiffness or tightness, and balance impairment.

Administering the questionnaires about emotion and behavior may be one of the more difficult parts of the evaluation. The information from these questionnaires comes through the filter of the subject’s own perceptions. Frequently, the goal is to take the subject’s answers and turn them into numeric values along some scale, thus quantifying the measurement. However, assigning values objectively to subject responses can be difficult and some of the responsibility ultimately rests with the judgment of the investigator asking the questions and recording the results. In an effort to make the process as scientifically objective as possible, numeric values along the scales are defined very specifically. Investigators must constantly struggle to ensure that results from these questionnaires are consistent across subjects and across testing sites.

Participant Rights^

Tempkin emphasized that careful consideration of participant rights is an integral part of running a study like COHORT. No potential participant is ever pressured into entering the study or enters without the most comprehensive knowledge of what the study entails. Before enrolling in the study, every potential participant must sign a consent form. The seventeen page long document can seem a little intimidating, but every effort is made to ensure that the potential participant reads and understands the entire form.

Tempkin explained that when the patient first expresses interest in participating, the form is mailed to his or her home address. This ensures that there is time to read over and think about the form in a no-pressure environment. If the potential participant still wants to enroll in the study, he or she will come in for the first visit. At this point, Tempkin will verbally review the consent form with the potential participant, making sure that there are no misunderstandings. The participant will only be enrolled once Tempkin satisfies herself that he or she fully understands and agrees to all of the conditions.

Consent forms are a key part of protecting participant rights in clinical trials. There are some aspects of the consent form that remain consistent across all UC Davis studies. For instance, the form starts out with the Experimental Subject’s Bill of Rights, which states explicitly many of the participant’s most important rights. For instance, every subject is entitled to know what the study is trying to discover, what procedures will happen to him or her during the course of the study, and what the risks and benefits of the study will be. Additionally, the bill of rights guarantees that the subject can stop participating at any time and that failure to participate will not impact future medical care.

The seventeen page length of this particular consent form is due largely to the complexity of the COHORT trial. Different aspects of the trial, such as the medical history and the tissue sampling, must be consented to separately from the trial as a whole. This ensures that participants are fully aware of everything to which they are consenting and grants more participant flexibility. If a subject wants to participate in the trial, but doesn’t want to share his or her medical history, this is possible. Tempkin mentioned, however, that patients in the HD community tend to want to participate as fully as possible in the trials, because they know the huge importance and potential benefits of research studies like COHORT.

More about Clinical Trials in the HD World and the Davis Center of Excellence^

Although our visit focused on the COHORT trial, the Davis COE is currently involved with several other HD clinical research trials. The Predict HD trial enrolls subjects who are gene positive for HD but have not yet developed symptoms. One defining feature of this trial is very lengthy neuropsychological testing administered by a trained physician as well as volumetric brain scanning. The goal is to search prospectively for early neuropsychological changes that occur before any motor changes.

Another study in which the Davis COE participates is PHAROS. This study enrolls subjects who are at risk for HD but have never been tested. The study is generally looking for precursors to HD phenotype expression and includes a heightened emphasis on mood evaluation.

For more about these studies, as well as other currently active HD trials, visit the Huntington Study Group here.

The UC Davis Center of Excellence typically conducts clinical research trials like COHORT and the ones described above once or twice a week at the VA Hospital in Rancho Cordova. The exact amount of time spent at the VA Hospital depends on how many trials are ongoing. During the rest of the week, the center is active in Sacramento at the UC Davis Medical Center, where they run an HD clinic and a Parkinson’s clinic.

The Collaborative Nature of HD Research^

During our visit, one point that came up again and again was the collaborative nature of HD research. From scientists conducting basic research, to doctors running clinical trials, the HD community is engaged in a cooperative venture. Information is shared freely between researchers and frequent communication allows for a coordinated research effort. This is a unique atmosphere in the world of academic research and it can be partly attributed to the strong, dedicated presence of the HD community. Researchers understand the stakes in the battle against HD and realize that the importance of their work demands the best possible effort. Cooperation is a key part of that effort.

A. Hepworth and A. Frohnmayer, 8-1-08
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The Washington University Medical Center in St. Louis Center of Excellence

In December of 2004, HOPES team members Kim Taub and Jia Hou visited Washington University in St. Louis, Missouri to get an inside view of an HDSA Center of Excellence. They met with Melinda Kavanaugh, a social worker in the Department of Neurology Movement Disorders Section, and Dr. Samer Tabbal, a neurologist.

Washington University Medical Center has been named a Center of Excellence by the Huntington’s Disease Society of America (HDSA). The HDSA recognizes those centers that provide excellent care for people with HD, participates in community outreach, and conduct research and clinical trials. Washington University serves more than the people of St. Louis; it reaches out to much of the Midwest.

Caring for HD^

The Center consists of a team of specialists, including several neurologists, a neuropsychiatrist, a social worker, a genetic counselor, and an occupational therapist. It is important that they approach their patients as a team because of the complicated nature of HD; people with HD often have several distinct medical complications that require specialized attention. For example, a neurologist may be able to help with choreonic (jerky, uncontrollable) movements, while a psychiatrist or licensed clinical social worker can assist in coping with potential psychological issues. A patient may also want to talk to a genetic counselor if he or she is considering having children. No single person is qualified to deal with all the facets of this disease. Consequently, it is best to approach and treat people with HD using a team of specialists who work together.

Melinda Kavanaugh, the Center’s social worker, met with Taub and Hou to explain how things work at Washington University. The team sees patients every Wednesday. Since the Center is located in the Movement Disorders section of the Department of Neurology, the team sees not only people with HD, but also people who have other diseases resulting in motor problems. Overall, the team sees about 2 to 8 people with HD each week. When patients come in, they first see Melinda to undergo cognitive testing using the Unified Huntington’s Disease Rating Scale (UHDRS).

Fig WU-1: Social worker Melinda Kavanaugh
Above: Social worker Melinda Kavanaugh next to the UHDRS computer.

Melinda made an important observation that is perhaps overlooked by the general population: “Primarily, I think this is a psychiatric disorder.” She explained that, most of the time, people with HD are not even aware of the erratic movements that they have. Instead, the things about the disease that bother them most include changes in mood, depression, the inability to control anger, and the frustrations arising from not being able to work. Because patients seem to be bothered most by mental as opposed to physical problems, the Center team focuses primarily on psychiatric and psychosocial aspects of HD. (Psychosocial is just what it sounds like; it involves how psychological aspects can affect social aspects of one’s life and vice-versa.) Rather than treating the movements right away, which they feel has historically been a huge mistake, the team instead focuses on family involvement, communication, and starting a chain of advocacy. They emphasize the importance of establishing good communication to prevent divorce and abandonment, which occur when family members do not understand their loved ones’ condition.

After seeing Melinda, the patients see Dr. Tabbal, a neurologist, for evaluations and referrals to occupational, physical, and speech therapists. Because HD can have a profound effect on a person, team members always recommend that their patients see a general therapist as well.

Community Outreach^

Besides seeing patients, the Center is especially active in reaching out to the greater HD community. Since the Center does not have its own HD facility, the team must attempt to reach “outside the clinic.” It is very difficult to find the type of specialized care offered at Washington University in the surrounding rural areas. Melinda and her coworkers therefore focus on extending care and education to these underserved areas. They travel to nursing homes to teach caregivers about HD and how to more effectively care for their patients. They also provide family and community outreach by placing ads in local papers and on local radio stations in rural areas, as well as by creating support groups to target these otherwise isolated populations.

Melinda explained that Dr. Joel Perlmutter, the Center Director, recognizes that the main impact of HD is psychosocial, that it can impede the socioeconomic development of families with this disease. This problem is especially devastating in farming communities with a tradition of large families. Large family sizes may result in concentrated clusters of HD, such as those found in southern Illinois.

Research at Washington University^

An important part of what makes the Washington University Medical Center a Center of Excellence is its participation in research on HD and clinical trials. Center Director Dr. Perlmutter has conducted much research on movement disorders. Dr. Perlmutter has published at least 100 articles in the past 20 years, the majority of which relate to Parkinson’s disease. (For more information on how Parkinson’s and HD are related, click here.)

Patients who come to the Center also have the opportunity to participate in national clinical trials. Two recent clinical trials are PREDICT-HD and the OX-Phos Study. PREDICT-HD is an observational study that tracks the progression of people with HD over the course of four years. When the participants come in for their visits, they undergo cognitive testing, MRI (Magnetic Resonance Imaging) scans of the brain, and a motor evaluation. The goal of this study is to find neurobiological predictors of HD; they are looking for some readily identifiable sign in the brain that will indicate the progression of HD.

The OX-Phos Study is named for oxidation-phosphorylation, a very important step in cellular energy production. This study examines people who have tested positive and negative for HD, but have not started to have symptoms or only have very mild symptoms. This study involves one or two patient visits to compare how people with HD use sugar and oxygen in the brain differently from people who don’t have HD. This study is important because it is known that the altered huntingtin protein causes problems with energy metabolism. By studying how oxygen and sugar (important ingredients in creating usable energy in the body) are used in the brains of people with HD, researchers can better identify metabolic problems and develop treatments to address them. (For more information of energy metabolism and HD, click here.)

Neurology at Washington University^

There are 400 people who work in the neurology department at Washington University. Dr. Tabbal, one of 40 clinicians at the Center, is also founder of the first HD clinic at the University of Arkansas. He is proud of the university’s prestige in the field: Washington University receives between 6 and 7 percent of the annual funding given by the National Institutes of Health (NIH), or roughly 22-23 million dollars.

Remarkably, the Positron Emission Tomography (PET) scanner was invented at Washington University. Although the original scanners were enormous, the ones used today are only slightly larger than the subjects that go in them, usually people and larger animals. PET scanners are a major research tool at the Center, something that distinguishes Washington University from other research labs.

Before PET was invented, researchers could only infer information about the brain through dissections after death and animal studies. PET allows researchers to track the function of the brain of a living, alert subject. To do this, a very small amount of a radioactive substance that is similar to a substance already found in the body is injected. As any radioactive substance decays, it emits particles called positrons. The scanner then picks up these positrons as the radioactive marker in the subject’s brain decays.

The specific kind of marker used depends on the area or function of the brain being studied. For example, a researcher studying glucose metabolism in the brain will inject a substance similar to a normal glucose molecule, but with an added radioactive fluorine atom, called TRIUMF. To study blood flow to various areas of the brain, radioactive water or 6-F-dopa is injected. The amount of radiation a subject is exposed to is typically less than he or she would be exposed to during an X-ray. Unlike X-rays, however, which produce only a shadow image, PET scans allow doctors and researchers to track changes in the subject’s brain as various cognitive tasks are performed.

Information gained from PET scans and genetic testing have contributed immensely to the growing body of knowledge on HD. Since 1992, when genetic testing became available for HD, scientists have been “learning exponentially” about the condition. Dr. Tabbal cautions that this knowledge must be used wisely.

“[Pharmaceutical companies] have a library of compounds,” says Dr. Tabbal, “Many are not FDA regulated. They are also expensive and ineffective, and we have little knowledge of their long-term effects. The difference between Western medicine and sorcery is that with Western medicine, we do research and experimentation to find out if there is validity to a drug’s proclaimed effect. Unfortunately, most of these drugs are more witchcraft than medicine.”

A drug that has recently gained publicity is Coenzyme Q-10. Q-10 supposedly prevents changes in nerve cells’ oxidation-phosphorylation, a normal metabolic process. These changes are believed to contribute to apoptosis of nerve cells, or nerve cell death. In clinical trials, only doses of 1200 mg have been shown to have any marked effect on persons with HD. Even then, the benefits are few. Dr. Tabbal points out that many people still pay a lot of money for doses of 50-100 mg.

According to Dr. Tabbal, the research conducted at the Washington University neurology department focuses on phenomenology, which means putting a great emphasis on understanding the process of disease rather than merely recording results. Otherwise, treatment becomes a shot in the dark.

Dr. Tabbal jokes, “There are more supporting staff [like Melinda] than doctors in the Movement Disorders department.” This high ratio of supporting staff to doctors is for a good reason. Like Melinda, Dr. Tabbal believes that HD is mainly a psychiatric disease which requires counseling as much as, if not more than, medical intervention to treat.

Dr. Tabbal is a friendly, upbeat doctor who has come close to experiencing the effects of HD firsthand. Every summer, he participates in a five-day camp for people with HD at Columbia University. Everything at the camp caters to people living with HD: the cabins are ergonomically designed and the daily schedule is highly structured and detailed.

“When you are surrounded by people with Huntington’s, you become the odd one,” Dr. Tabbal says. “It is the only way you can really understand what’s it’s like. You understand why it takes so long to dress, how they fall.”

Dr. Tabbal believes that a good support system, physical therapy, relevant medicines, and the right attitude should be the foundation of treatment. He believes that there is hope after a diagnosis of HD. People at risk for HD should not be afraid of what the doctor might say because, after all, the diagnosis is the first step in treatment. Dr. Tabbal adds his final piece of advice with a smile, “Make sure you see a good doctor.”

For further reading^

  1. To find out more about HDSA Centers of Excellence, visit http://www.hdteam.org/coe.shtml.
  2. To find out more about the Washington University Center of Excellence, visit the website at http://neuro.wustl.edu/patientcare/clinicalservices/movementdisorders/huntingtonsdisease/.
  3. To find out more about PREDICT-HD, visit http://clinicaltrials.gov/ct/show/NCT00051324?order=1.

-K. Taub, 1-29-06
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Johns Hopkins Center of Excellence

In April 2007, HOPES researcher Justine Seidenfeld visited the Baltimore Huntington’s Disease Center (BHDC) in the Department of Psychiatry at the Johns Hopkins University School of Medicine in Baltimore, MD. The BHDC has been designated as a Center of Excellence by the Huntington’s Disease Society of America (HDSA). Centers of Excellence are recognized not only for the quality and scope of care they provide for their patients, but also for their clinical and basic research efforts, and the outreach services they provide to the general community. For more on the HDSA’s Center of Excellence program, please click here. The Baltimore Huntington’s Disease Center serves most of the mid-Atlantic region, providing services to Maryland, Pennsylvania, Delaware, New Jersey, Washington DC, and Virginia.

HOPES would like to thank the Baltimore Huntington’s Disease Center, particularly Mr. Abhijit Agarwal, Ms. Kit McFarland, Ms. Debbie Pollard, and the director of the Center, Dr. Chris Ross, for taking time out of their busy schedules to speak with us and share their perspectives on Huntington’s disease research.

Clinical Programs^

The Baltimore Huntington’s Disease Center is the only HDSA Center of Excellence based in a psychiatry department (instead of a neurology department) of a medical school or hospital. As such, the Center can pay special and expert attention to treating the psychiatric and psychosocial aspects of the disease, for which we now often have effective symptomatic treatment. However research focuses mostly on brain imaging, neurobiology, genetic mouse models and other basic science, and clinical trials of new therapeutic agents. For more information on the symptoms of HD, click here.

Ms. Debbie Pollard is the clinic coordinator at the BHDC, and she helps patients when they first come to the Center. Ms. Pollard performs full physical exams for each patient to initially determine what symptoms they have, takes a full family and personal health history, and helps to generally guide patients as to how the center works and what services they provide.

The Center runs two separate multidisciplinary clinical programs to provide services to incoming HD patients. Additionally, there are related social services (such as community resource referrals and housing assistance) available in both programs. Confidentiality is strictly upheld in all cases and practices.

One of the clinical programs is an “Evaluation and Research” program, which runs every Tuesday from 1-4pm. The program is over 25 years old, and is supported by the HDSA and the National Institutes of Health (NIH). Thanks to these research grants, all of the services are (presently) provided with no charge. Patients can either make an appointment to come in on their own, or they may be referred to the Center by other physicians or neurologists in the area. At the first meeting, a number of neurological and psychiatric evaluative tests are conducted in addition to the detailed medical and family history that Ms. Pollard takes. Individuals who do not know if they have the altered huntingtin gene, but are presenting some of the symptoms of HD, can take a genetic test for HD (or other potential neurodegenerative disorders) if they so wish. Other staff members of the BHDC may see the patients for follow up services like consultations, case management (including symptomatic treatments for chorea or anti-psychotics if appropriate), counseling, and referrals if it is necessary.

The second clinical program offered at the Baltimore Huntington’s Disease Center is the “Continuing Care Program”. This program offers ongoing medical care for HD patients, as well as counseling and social services for them and their families. The primary purpose of the clinic is to treat and manage HD symptoms through medication, counseling, and to help patients to adjust their environmental surroundings. Patients can be referred to see staff members at the center who serve as neuro-psychiatrist specialists, social workers, or be referred for occupational therapy and speech therapy. The goal of the staff is to work with patients and their families to develop a tailored program for care. As opposed to the “Research and Evaluation” program, services from this program must be paid for, but health insurance is accepted when it applies. However, a generous grant from the HDSA allows the BHDC to charge for services based on the patient’s ability to pay and provide services for free to individuals that cannot otherwise afford it.

The clinic also conducts genetic tests for family members of those with HD who want to know their gene status. Genetic testing is a serious issue, and should only be undertaken after much consideration and counseling- for more information about genetic testing for Huntington’s Disease, please click here. They also offer counseling to many asymptomatic individuals who have the altered HD gene, in order to help them adjust to the kinds of lifestyle changes they can anticipate when symptoms begin to appear. Ms. Pollard emphasizes that as a Center of Excellence, the clinic is open to anyone regardless of the ability to pay, so anyone may come in for these services.

Social Services^

Social worker Ms. Kit McFarland explains that the BHDC is mostly a research operation that also provides care to patients. A large part of Ms. McFarland’s job is to provide tailored information about HD to families or individuals who have specific concerns. She also puts together an initial package of basic information for those who are unfamiliar with HD to use before they need more specialized help. Much of the time, the people who come to her for advice are families who have just learned that HD runs in their family (usually after one member was diagnosed with it) and they desire more information.

Ms. McFarland feels her job as a clinical social worker is to generally help people learn how to best support and stay involved with their family members that have been diagnosed with HD. For example, she gives them tips to help them make certain that the member of the family with HD stays well-nourished, such as using Ensure shakes. For family members who act as caregivers, she often finds that it is difficult for them to understand how their loved one will change behaviorally throughout the course of the disease, and so she tries to provide ways for them to cope with this issue. They may commonly encounter violent reactions from the family member with HD, but sometimes it can be hard to tell if it is intended violence or a motion from chorea. For those afflicted with HD, one of the most difficult parts of the disease is the gradual loss of their freedom- particularly when in comes to driving. If it comes time for the HD patient to stop driving but they refuse, Ms. McFarland might tell the family members or caregiver that the patient needs to be taken for a driving test, and tries to get the family involved in this decision. For more on HD and driving, please click here.

Another one of Ms. McFarland’s chief tasks is to provide help to the outside community, particularly those who have reached the stage of HD where they need some kind of assisted living arrangement- either in nursing homes or other facilities. This is a difficult process because many individuals with HD are often not prepared to relinquish their independence, even when it is necessary. She also works directly with employees of nursing homes and assisted living facilities in the area to teach them skills they need to serve residents with HD. She explains that many of the issues that nursing home or assisted living facility employees will encounter with their HD residents are actually very common among individuals of that age- such as problems with getting residents to eat. The major differences in residents with HD, that pose greater problems to the staff, are very rapid weight loss and aggression. For more on the manifestations of aggression in HD, click here. Ms. McFarland is also highly involved in much of the Center’s efforts to provide help, information, and services to those patients who have difficulties with transportation and cannot come to the center themselves.

Clinical Trials^

Mr. Abhi Agarwal is the clinical research coordinator for the BHDC, and his job is to organize the enrollment and participation of patients in various clinical trials run through the Center. As Mr. Agarwal explains, the Center offers a wide range of opportunities for individuals and their families to participate in a variety of clinical research studies. Participation in these research trials is free of charge, thanks to a number of research grants from the National Institutes of Health (NIH), the Huntington’s Disease Society of America (HDSA), and the Huntington’s Disease Foundation (HDF).

Mr. Agarwal explains that they take a diverse array of approaches to looking at HD, conducting clinical studies that involve genetics, neuropathy, autopsy-based studies, fMRI studies, and basic research studies. He elaborates further on the clinical research studies currently being conducted at the Center:

1) The Longitudinal Core Study: This project is an observational study, which means that it is not intended to test potential treatments for HD, but rather is a study that will help advance our understanding of the natural onset and progression of HD. To enroll in the trial, the only requirement is to have undergone testing for the altered HD gene- participants don’t need to actually have HD, because control subjects are needed as well. Any patient that participates in the study at the BHDC is seen annually from their enrollment until their death, and at each yearly meeting they receive full neurological and psychological evaluations to assess the how far along motor, cognitive, and behavioral symptoms have progressed. They also receive functional magnetic resonance imaging, or fMRI scans on every other visit to look for structural differences in the brain over time (changes in the shape of the brain, usually related to nerve cell death), and to compare this to people who do not have HD. Because longitudinal studies often require large numbers of patients, the other goal for this study is to assemble a large database of patients who may be able to simultaneously participate in other clinical trials for HD. The Center has about 90 – 110 participants a year for this study.

Mr. Agrawal emphasizes that for observational longitudinal studies to get results, it takes time to be able to see statistically significant patterns that will further the understanding of HD. But these studies can provide critical information on the disease. For instance, the center has been able to demonstrate using sophisticated brain imaging, that striatal atrophy begins at least 10 years prior to clinical onset, that neuronal cell death correlates best with functional disability, and that the number of trinucleotide repeats in the huntingtin protein has an effect on the rate of HD progression. They found that individuals with the smallest number of trinucleotide repeats appear to have the best prognosis. For more about trinucleotide repeat lengths and the huntingtin protein, click here.

2) Genetic study for Huntington’s Disease-like 2 : Researchers at the Baltimore Huntington’s Disease Center are also very interested in looking for other genes that cause HD-like diseases. They have actually identified a number of these disorders, which are defined by having very similar symptoms to HD, but do not involve the altered HD gene- the HD gene can be perfectly normal and these symptoms may still appear. One of these diseases is called Huntington’s Disease-like 2 (HDL-2) and like HD, it is an adult onset neurodegeneration disorder, it is autosomal dominant, and it is characterized by chorea, cognitive, and psychiatric symptoms. It also involves neurodegeneration and inclusion bodies in the same parts of the brain as in HD. The Center is now working on a project to identify genetic markers for this disease, and to understand what kinds of mutations (other than the altered huntingtin mutation) could cause a disease like HD. They have recently published a paper in 2007, linking HDL2 to a glutamine/CTG repeat mutation on chromosome 16. This kind of mutation is related to, but not the same as the mutation involved in HD. They hope that by understanding the pathology behind HDL-2, it will shed new light on the pathology of HD and other neurodegenerative diseases.

3) Huntington Study Group trials : The BHDC participates in a number of multi-site clinical trials run by the Huntington Study Group. The Huntington Study Group is a non-profit organization composed of physicians, medical researchers and health-care providers from around the world. They have been organizing and conducting clinical trials for HD since 1993. In particular, the Center recruits participants for the observational PHAROS and COHORT studies, the PREDICT-HD study to find neurobiological markers of HD, and the completed TREND-HD study which is a therapeutic trial for Ethyl-EPA. For more on the Huntington Study Group, please click here, and for information on clinical trials in HD, please click here.

4) Memantine Study : The Center is also conducting a clinical trial with memantine, a drug that has already been approved by the FDA and marketed as Namenda for use in Alzheimer’s disease patients. However, not much is known about its use in HD, so the purpose of this clinical trial is to test if it will improve or delay cognitive symptoms of HD. The trial is sponsored by a company named Forest Pharmaceuticals, a company that produces drugs for cardiovascular diseases and CNS diseases like HD. This type of trial is a new indication study, and so it is run as a double-blinded, placebo trial over the course of 6 months. The Baltimore Huntington’s Disease Center started recruiting patients for this study in the fall of 2006, and as of March 2007 they have 72 participants. For more information on the use of memantine in HD, click here.

While anywhere from 150-200 people come in for clinical services in an average year, 2006 was an especially busy year for the clinic. Mr. Agrawal also explains that while many people come to the BHDC for genetic testing or patient care, about 25% to 50% of those who come also agree to participate in the clinical trials run through the Center. A good reason for any individual with HD to participate in the Longitudinal Core Study run at the Center is that there will be records of them kept in the Center’s database system, and so they can potentially be contacted to be recruited for any new therapeutic clinical trials if they fit the criteria needed to be included in the study.

Basic Research^

Dr. Chris Ross is the director of the Baltimore Huntington’s Disease Center, and runs a research laboratory that focuses on the neuronal biology and genetics of neurodegenerative and psychiatric disorders such as HD, Parkinson’s disease, schizophrenia.

Dr. Ross discusses a few of the research projects conducted in his laboratory. He explains that the primary purpose of basic research is to identify biological targets for HD, and to develop those targets into treatments. For more on the process of going from basic research to a treatment, click here. As such, his lab focuses their research projects around potential biological targets for HD, and mostly on the huntingtin protein itself.

1) One area of current studies focus on how huntingtin aggregates are formed, and at what point these aggregates are toxic and cause nerve cell death. They have hypothesized that the larger aggregates or neuronal inclusions are not the most toxic molecules, but rather that the intermediates proteins in this aggregation pathway (the early aggregates) may be the most lethal form. As such, they may be the best molecules to target for future therapies. For more information on huntingtin aggregation, please click here.

Dr. Michelle Poirier, another faculty member at Psychiatry at the Johns Hopkins University School of Medicine, is doing studies in her own laboratory to investigate the shape or molecular structure of these intermediate huntingtin proteins. One of the most recent theories of how huntingtin protein aggregates are shaped describes them as made up of a series of folded strands of amino acids, with each strand composed of seven or eight glutamine amino acids. In a paper published in 2005, Dr. Poirier collaborated with the Ross lab to create two tissue culture models based on this theory. They confirmed that the proposed structure does indeed occur, and that there is a correlation between the presence of this type of huntingtin aggregate in the tissue culture cell and the presence of cell toxicity. However, they suggest that it is entirely possible that the toxicity is not caused directly by these aggregates, but rather that any of the kinds of intermediate species formed throughout the aggregate pathway may be responsible for toxicity instead.

2) Another project in the Ross lab looks at what kinds of proteins are involved in cutting the huntingtin protein into fragments. This process is also implicated in nerve cell toxicity in HD – it is thought that a fragment of huntingtin is actually more toxic to the cell than a full-length huntingtin protein. For more information on huntingtin protein fragments, please see figure P-2 here. In collaboration with Dr. David Borchelt and his laboratory at the University of Florida’s College of Medicine, Dr. Ross’ lab developed one of the initial transgenic mouse models of HD. Dr. Ross’s lab has used this mouse model to look at which enzymes play the largest role in generating toxic fragments of huntingtin protein. In collaboration with Dr. Michael Hayden’s laboratory they have already determined that caspase-6 is one of the most commonly involved enzymes in huntingtin fragmentation (please click here for a HOPES article on that finding), but they are looking at the role of other caspases and calpains (another family of proteases) as well.

Tamara Ratovitski, a member of the Ross lab, leads a related project using tissue culture models to look for the specific points in the chain of amino acids in the HD protein where fragmentation occurs. She wants to understand exactly how many fragments are generated by each type of protease, and how long they are. The goal is to target the most important proteases for inhibition, which will reduce the number of fragments and (presumably) cell toxicity.

3) A third project at the Ross lab looks at the affects of the mutant HD protein upon gene transcription. It is thought that the altered huntingtin protein changes the patterns of how genes are transcribed and translated, especially the genes that are key for a cell’s survival- and this may contribute greatly to toxicity in HD. Several years ago, Dr. Ross’ lab identified an unusual interaction between the mutant HD protein and the CREB-binding protein (also known as CBP), a smaller regulatory protein that is key for cell survival. For more information on the role of CBP in HD, click here.

Currently, the lab is following up this project with another group of studies intending to demonstrate a direct connection between the altered huntingtin protein, altered gene transcription, and cellular toxicity. It may be that the interaction between CBP and the altered huntingtin protein is one of a group of similar interactions between proteins involved in gene transcription and the altered huntingtin protein. If their research conclusively demonstrates that altered gene transcription does lead to cellular toxicity, one possible therapeutic intervention would be to use HDAC inhibitors. For more information on the potential role for HDAC inhibitors, please click here.

When asked what he thinks about the role of basic scientific research in respect to the larger body of HD research, Dr. Ross illustrates his opinion by discussing what goes on at the Baltimore Huntington’s Disease Center. Dr.Wenzhuan Duan, an assistant professor in the Department of Psychiatry and Behavioral Sciences works on research in Huntington’s and Parkinson’s disease. He takes biological targets identified through basic research on HD, and develops potential therapeutic drugs based on these findings. For more information on the process of drug research and development in HD, click here. They have developed a tissue culture model using nerve cells with the altered huntingtin protein that can be used to test potential therapeutic compounds to see if they might be useful for treating HD.

Dr. Ross emphasizes that another one of the major goals in doing therapeutic research is not only to cure HD, but to delay its onset. The idea would be to intervene by using treatments before the cognitive, motor, or behavioral symptoms actually appear. Members of the BHDC have already demonstrated that a great deal of neurodegeneration occurs before symptoms actually appear, so it would be effective if treatment occurred before the identifiable “onset” of symptoms to prevent or delay them. The Center has submitted a grant to conduct a phase II clinical trial to look at the effects of coenzyme-Q10 on presymptomatic HD patients, to see if it does in fact, delay the onset of symptoms. For more information of co-enzyme Q-10, please click here. The focus on research and treatments for presymptomatic HD patients is a very new direction for the Center, and appears to be a promising one.

For further reading^

  • The Baltimore Huntington’s Disease Center.
    The website for this HDSA Center of Excellence.
  • Rosenblatt A, et al. The association of CAG repeat length with clinical progression in Huntington disease. Neurology. 2006;66(7):1016-20.
    This study demonstrates that individuals with the smallest number of trinucleotide repeats appear to have the best prognosis
  • Reading S, et al. Functional Brain Changes in Presymptomatic Huntington’s Disease. Ann Neurology 2004;55;879-883
    The 2004 publication demonstrating that there are significant structural changes in the brain in presymptomatic HD patients.
  • Rudnicki DD, et al. Huntington’s Disease Like-2 Is Associated with CUG Repeat-Containing RNA Foci. Ann Neurology 2007;61;272-282
    A follow-up study on HDL-2 demonstrating that it affects RNA function, and this may contribute to cell toxicity in HDL-2.
  • Schilling G, et al. Characterization of Huntingtin Pathologic Fragments in Human Huntington Disease, Transgenic Mice, and Cell Models. J Neuropathology 2007. Vol 66, No. 4; 313-320
    This publication demonstrates the location of significant sites of huntingtin fragmentation.
  • Poirier MA, et al. A Structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure. Human Molecular Genetics, 2005. Vol. 14, No.6: 765-774.
    This paper discusses the models for huntingtin protein aggregate structure, and further confirming the beta-strand/beta-turn model of aggregation.
  • Wang W, et al. Compounds blocking mutant huntingtin toxicity identified using a Huntington’s disease neuronal cell model. Neurobiology of Disease. 2005;500-508.
    This paper discusses a tissue culture model that has been demonstrated to be a good method to screen potential therapeutic compounds for treating HD.

-J. Seidenfeld, 8/21/2007
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About HDSA Centers of Excellence

This chapter explains what it means to be an HDSA “Center of Excellence”. We begin with a brief description of HDSA, the organization that names Centers of Excellence. Next we describe many of the services that the Centers of Excellence offer. We include a description of what an HD patient could expect during a first visit to a Center of Excellence clinic. And finally, we give a full list of the HDSA Centers, with contact information for each.

The Huntington’s Disease Society of America^

There are nineteen HDSA Centers of Excellence located in the United States.

All of these Centers have specialized HD programs and reputations for first-rate treatment. But how are they chosen and what exactly is required to become a Center of Excellence?

Centers of Excellence are chosen by the Huntington’s Disease Society of America (HDSA). HDSA is a national nonprofit health organization dedicated to finding a cure for Huntington’s Disease and to providing support for everyone affected by HD – both patients and their families. For more information about HDSA, or to contact HDSA, click here.

By recognizing some of the best HD clinics in the nation, HDSA hopes to promote the highest standards of care. To qualify as a Center of Excellence, an HD clinic must provide comprehensive services, have a reputation for excellent medical care, and demonstrate a commitment to HD education and research.

What it means to be an HDSA Center of Excellence^

All Centers of Excellence maintain an active HD clinic. The clinic not only serves patients already diagnosed with HD, but is also equipped to provide pretest counseling and genetic testing. Centers of Excellence typically have a staff of specialists who can help with issues specific to HD. For example, many Centers have physical therapists, neurologists, genetic counselors and speech therapists. This specialized staff is not the only reason why Centers of Excellence are especially qualified to treat HD. Everyone working at the Center also has a familiarity with the disease. The Staff at Centers of Excellence know what individuals with HD and their families need based on extensive experience. The Centers also always have the most recent and accurate information available.

Additionally, every Center of Excellence can offer patients the opportunity to participate in clinical trials and other HD research opportunities. Many centers are part of the Huntington’s Study Group (HSG). HSG is a nonprofit group of healthcare providers based in the United States, Europe, Canada, and Australia who join together to conduct clinical research trials. By organizing and coordinating research across large numbers of sites, HSG can conduct comprehensive clinical trials. To visit the HSG website, click here. Participating in clinical trials can be a way to contribute to the HD community and become part of the effort to improve the lives of those affected by the disease.

All HDSA Centers of Excellence engage in educational outreach. The centers have several ways of providing information about the disease. Centers will usually have comprehensive literature available at the clinic for patients. This can be especially helpful for individuals who have recently discovered they have HD. Additionally, some centers hold conferences where many groups and individuals can gather and exchange information. These conferences let researchers, doctors, organizations and others committed to treating and caring for HD patients stay on the forefront of the latest research findings. Finally, many Centers attempt to share their expertise with other medical workers caring for HD patients. For instance, the Center can send staff directly to local nursing homes to provide HD specific training, information, and assistance to the nursing home staff. This outreach is an important aspect of the Centers’ mission to provide care and service to the HD community.

The Role of the HD Clinic^

Many newly diagnosed HD patients do not know what to expect from an HD clinic. The thought of going to a clinic specifically focused on HD can seem intimidating and daunting. The goal of this section is to give a brief description of what happens during a first time visit to an HD clinic. Hopefully, this knowledge will help make the experience easier and more comfortable for everyone involved.

In many ways, going to an HD clinic is much the same as a normal doctor’s visit. The main difference is that the clinic staff members are guaranteed to have specialized knowledge about HD. Although the staff will always tailor treatment to the individual patient, they have a broad base of experience to draw upon; they understand what it means to have HD and to be at risk for HD. Additionally, the clinic may have resources helpful to HD patients that a regular doctor wouldn’t have (such as HD-experienced physical therapists, social workers, genetic counselors, etc.).

During a first visit the patient will always see a doctor. They may or may not see other HD specialists depending on individual circumstances. Most of the time they will see other specialists during follow-up visits. The length of time between visits varies dramatically depending on individual circumstances. If the doctor decides that only a routine follow-up visit is required, the next visit may be scheduled for one year later. If the doctor has a specific issue he or she wants to address, a follow-up visit may be scheduled as soon as one month later. There is no standard length between visits – it is entirely dependent on the patient’s needs and desires.

Finally, HD clinics at Centers of Excellence are active in current clinical trials. This is one of the requirements a clinic must meet to be chosen as an HDSA Center of Excellence. Depending on the status of ongoing trials, the clinic could offer patients the opportunity to participate. These clinical trials provide a chance to contribute to HD research. The exact nature of the available trials will vary from clinic to clinic and change over time.

We hope patients, or potential patients, will not feel intimidated by the idea of visiting an HD clinic. The clinics exist to help and support the patients and their families. Clinic doctors and personnel understand the difficulties of living with HD and their goal is to offer the best care available. We suggest that everyone in the US with HD and their families consider a visit soon to an HD Center of Excellence, if they haven’t already.

List of HDSA Centers of Excellence^

For an interactive map, listing HDSA centers of excellence by state, click here.

Northeast^

New England HDSA Center of Excellence
Charlestown , MA 02129
Director: Steven Hersch, M.D.
Center Contact: Jamie Hill
Phone: 617/724-2227
Email: jhill11@partners.org

Website: http://www.mgh.harvard.edu/neurology/services/treatmentprograms.aspx?id=1048

HDSA Center of Excellence at the University of Rochester
Rochester , NY 14620
Directors: Kevin Biglan, M.D., MPH and Frederick Marshall, M.D.
Center Contact: Leslie Briner
Phone: 585/273-4147
Email: leslie.briner@ctcc.rochester.edu

HDSA Center of Excellence at Columbia Health Sciences/NYS Psychiatric Institute
New York , NY 10032
Directors: Karen Mardner, M.D.
Center Contact: Debbie Thorne
Phone: 212/305-9172
Email: thorned@sergievsky.cpms.columbia.edu
Website: http://www.hdny.org/

George G. Powell HDSA Center of Excellence at North Shore University Hospital
Manhasset , NY 11030
Director: Andrew Feigin, M.D.
Center Contact: Patricia Lambert
Phone: 631/234-0136

HDSA Center of Excellence at Johns Hopkins University/Johns Hopkins Hospital
Baltimore , MD 21287
Directors: Christopher Ross, M.D., Ph.D. and Adam Rosenblatt, M.D.
Center Contact: Debbie Pollard
Phone: 410/955-2398
Email: dpollard@jhmi.edu

HDSA Center of Excellence at the University of Virginia
Charlottesville , VA 22903
Director: Madaline Harrison, M.D.
Center Contact: Pat Allinson, M.S.
Phone: 434/924-2665
Email: psa9m@hscmail.mcc.virginia.edu

Southeast^

HDSA Center of Excellence at Emory School of Medicine
Atlanta , Ga. 30329
Directors: Randi Jones, Ph.D. and Claudia Testa, M.D., Ph.D.
Center Contact: Joan Harrison, G.N.P.
Phone: 404/728-6364
Email: jharri2@emory.edu

HDSA Center of Excellence at University of Alabama
Birmingham , Ala. 35294
Director: Leon Dure, M.D.
Center Contact: Stacey Mantooth
Phone: 205/996-7850
Email: smantooth@peds.uab.edu

HDSA Center of Excellence at the Univeristy of South Florida Huntington’s Disease Clinic
Tampa, FL 33612
Director: Juan Sanchez-Ramos
Center Contact: Kelly Elliott, RN
Phone: 813/974-6022
Email: kelliot@health.usf.edu

Midwest^

HDSA Center of Excellence at Ohio State University
Columbus , Ohio 43210
Director: Sandra Kostyk, M.D., Ph.D.
Center Contact: Nonna Stepanov
Phone: 614/688-8672
Email: stepanov-1@medctr.osu.edu

HDSA Center of Excellence at University of Iowa Hospitals and Clinics
Iowa City , Iowa 52242
Directors: Jane Paulsen, Ph.D. and Robert Rodnitsky, M.D.
Center Contact: Anne Leserman
Phone: 319/353-4307
Email: anne-leserman@uiowa.edu

HDSA Center of Excellence at Hennepin County Medical Center
Minneapolis , MN 55415
Director: Martha Nance, M.D.
Center Contact: Dawn Radtke, RN
Phone: 612/873-2943
Email: Dawn.radtke@yahoo.com

HDSA Center of Excellence at Washington University School of Medicine
St. Louis , MO 63110
Director: Joel Perlmutter, M.D.
Center Contact: Stacey Barton, MSW, LCSW
Phone: 314/362-3471
Email: bartons@neuro.wustl.edu

HDSA Center of Excellence at Rush University Medical Center
Chicago , IL 60612
Director: Kathleen M Shannon, M.D.
Contact: Jean Jaglin, RN, CRC
Phone: 312/942-5003
Email: Jean_A_Jaglin@rush.edu

HDSA Center of Excellence at Indiana University
Indianapolis, IN 46202
Directors: Kimberly A Quaid, Ph.D and Joanne Wojcieszek, M.D.
Contact: Leo Rafail, BSW
Phone: 866/488-0008
Email: info@iuhdclinic.org

West and Pacific Northwest^

HDSA Center of Excellence at Colorado Neurological Institute
Englewood, CO 80113
Director: Rajeev Kumar, M.D.
Center Contact: Mimi Ortiz
Phone: 303/357-5453
Email: ortiz@kumarneuro.com

HDSA Center of Excellence at University of Washington
Seattle , Wash. 98195
Director: Thomas Bird, M.D.
Center Contact: Debbie Olsen (general info)
Phone: 206/616-2135

Southwest^

HDSA Center of Excellence at University of California Davis Medical Center
Davis Medical Center
Sacramento , Calif. 95817
Directors: Vicki Wheelock, M.D.
Center Contact: Teresa Tempkin R.N.C., M.R.N., A.N.P.
Phone: 916/734-6278
Email: teresa.tempkin@ucdmc.ucdavis.edu

HDSA Center of Excellence at University of California, San Diego
San Diego , Calif. 92103
Directors: Jody Corey-Bloom, M.D., Ph.D.
Center Contact: Jody Goldstein
Phone: 858/622-5854
Email: jlgoldstein@ucsd.edu

HDSA Center of Excellence at University of California, Los Angeles
Los Angeles , Ca 90095
Director: Susan L Periman, M.D.
Center Contact: Sakena Patterson
Phone: 310/794-1225
Email: sjpatterson@mednet.ucla.edu

HDSA Center of Excellence at Baylor College of Medicine
Houston , Texas 77030
Director: Joseph Jankovic, M.D.
Center Contact: Alicia Palao
Phone: 713/798-7438
Email: palao@bcm.edu

For Further Reading^

-A. Hepworth, 1-24-07, updated 6-21-11

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HDSA Center of Excellence at Columbia University

HDSA Center of Excellence at Columbia University
New York State Psychiatric Institute
New York, NY

In the summer of 2005, HOPES researchers Jia Hou and Clare Tobin visited the HDSA (Huntington’s Disease Society of America) Center of Excellence at Columbia University in New York, NY. Hou and Tobin would like to thank everyone at the center for taking the time to speak with them on an especially busy day. They would also like to thank the patients who gave such candid interviews and permitted us to observe their evaluations. To visit the Columbia center’s website, click here.

Introduction^

The HDSA Center of Excellence at Columbia is a highly specialized program. It is primarily a clinical facility, but medical research is a very important part of the center’s mission as well. When patients come to the center, they are screened as possible participants for the many HD-related research studies that are conducted elsewhere in the hospital. Patients may choose whether or not to participate; either way, they receive high quality care.

Because HD is such a complex disease to manage, the center provides many different kinds of specialists and medical services. Hou and Tobin were able to meet several members of the center’s interdisciplinary team, including:

Karen Marder, MD, MPH – Neurologist (and Center Director)
Mark Groves, MD – Psychiatrist
Jeanne Thomson, MS, CCC-SLP – Speech Therapist
Ashwini Rao, Ed.D, OTR – Occupational (and Physical) Therapist
Deborah Thorne, LCSW – Social Worker
Jennifer Williamson-Catania, MS – Genetic Counselor
Paula Leber, MA – Research Assistant
To read more about these staff members and the rest of the staff, click here.

A significant part of the center activities revolve around people who are at risk for HD, but are not symptomatic. These people have a family history of HD, but do not know if they carry the HD allele. One way to determine this is with predictive genetic testing. (For more information on testing, click here). For issues surrounding predictive testing, Hou and Tobin spoke with Jennifer Williamson-Catania, the center’s genetic counselor. More information on this topic will be discussed later in the chapter. In the meantime, the focus will be on the organization of the center and how it helps those with HD.

The Clinic^

HOPES visited the Columbia center on August 19th, 2005 to observe one of their monthly clinic days. On these special clinic days, many patients come into the center. The team of specialists that comprise the center’s comprehensive care program will then re-evaluate each patient’s disease progression. On their first visit, patients meet with the entire team of specialists, and then usually come in two times each year after that. Patients may come in more often, depending on the progression of their condition. The medical team consists primarily of a psychiatrist, neurologist, speech therapist, occupational/physical therapist, and social worker. The team meets with each patient (and usually his or her primary caregiver) to examine the patient’s current health status. The patient may then meet with individual specialists to discuss specific adjustments to treatment and lifestyle. For example, speech therapist Jeanne Thomson may recommend getting speech therapy a few times a week for a number of months. Speech therapy can help with communication, especially over the phone, as well as problems with eating. It is very important to address eating issues because coughing, choking, and aspiration pneumonia are serious concerns for people with HD. (For information on aspiration pneumonia and other complications of HD, click here). For patients that do not live near the center, Ms. Thomson refers them to therapists who work in their area. There is a similar procedure for physical therapy and other forms of therapy. The team may prescribe medications that alleviate symptoms, but there is no medication that can treat the disease itself. In general, the team recommends against taking any kind of dietary supplements for the purpose of treating HD.

For all patients, care at the center is free of charge. This situation certainly eases the burden on families, makes it possible for patients to receive the care that they need without financial constraints, and better protects confidentiality by avoiding involvement with insurance companies. However, patients still face other costs, such as hiring home health care aides or receiving treatment for other conditions. For these reasons, the center is quite concerned with health insurance issues. The people at the center help patients figure out how to afford the other aspects of their care by considering alternative resources, such as Medicaid, Medicare, and disability insurance.

Resources and Support^

The center provides many resources beyond those of standard clinical care. There are many specialists available for consultation, as well as other HD patients for mutual support. The center has a large body of HD-related literature for patients to read. There is an at-risk support group and an early-to-middle stage patient support group that each meets once a month at Columbia. Other support groups meet at different nearby New York locations. The center takes part in many events throughout the year that raise money for HD research, from amaryllis bulb sales to a BMW sweepstakes and “Hoop-a-thons.” Hou and Tobin were fortunate during their visit to meet a young boy and his family who helped raise a large sum of money for HD research; they were inspired to coordinate such an effort because of a neighbor that had been affected by HD. (For more information on upcoming events at the center, click here).

Another way that the center improves the lives of people with HD is through their annual camp, which was started in 1993. During the summer, 14-18 patients spend a week in Cornwall-on-Hudson, NY with camp staff. Many members of the camp staff also work at the Columbia center. At camp, everyone takes part in all sorts of activities, from singing to horseback riding to pool volleyball. This special week gives patients a chance to have fun, spend time with others who understand what it is like to have HD, and bond with people from the center. The week also provides a well-deserved vacation for caregivers. (For more information on the HD Summer Camp Program, click here).

Research^

Though the Columbia center is primarily a clinical facility, they also conduct important medical research. Patients often choose to become involved in research studies or clinical drug trials to help advance scientific knowledge about HD. Because HD tends to run in families, many patients are particularly concerned about finding effective treatment, even if not for themselves. During the HOPES visit, Hou and Tobin were able to observe the preliminary stages of a research project that uses fMRI scans to try to find early changes in the brain that are associated with HD. The study compares the scans of presymptomatic and symptomatic individuals (people who have HD) and controls (people who do not have HD). Several patients from the center volunteered for the scans, and several of their spouses volunteered as controls.

Hou and Tobin were also invited to sit in on a lunchtime presentation given by a Columbia medical student who had been researching HD. First, he discussed dietary supplements and HD. There have been many reports about the effectiveness of various supplements in combating the progression of HD. Sometimes these reports are exaggerated by people outside of the medical community who are well-meaning but impatient for a cure. The student’s presentation showed that, while some supplements show promise, there is no evidence of benefits at this time. This is why the center’s team recommends against taking supplements for the treatment of HD. (For more information on dietary supplements, click here). Hou and Tobin were proud to note that the information in the presentation had already been evaluated and posted on the HOPES website prior to their visit.

The second part of the presentation was about driving and HD, a common and serious concern for patients and their families. At a certain point in the progression of the disease, it may no longer be safe for people with HD to continue to drive. However, this can mean a loss of independence and self-sufficiency, which makes it a very difficult decision. If there is concern about a patient’s ability to drive, the team may recommend an independent driving evaluation. Though many people with HD continue to drive successfully for a long time, driving and HD is a very important issue which needs to be more widely discussed in the HD community.

Bridging the Medical and Social Aspects of HD Care^

In addition to managing the physical symptoms of HD, a good clinical facility also needs to consider the psychosocial and overall well-being of its patients. What sets the Columbia center, and other Centers of Excellence, apart from standard treatment is how the teams there provide comprehensive care. In addition to making a diagnosis, assessing symptoms, and recommending treatments, the clinical team considers factors such as a patient’s access to continuing care, sources of funding, and concurrent medical conditions.

The center’s team also helps patients make informed decisions about various aspects of their lives, while respecting their autonomy. For example, it can be very difficult for someone with HD to give up daily activities like driving, but these decisions eventually need to be made. Yet it is difficult to determine exactly when to make these decisions, given the gradual progression of the disease. Comprehensive, individualized care from the team can help people with HD and their families make important decisions.

Families affected by HD must also make decisions about predictive genetic testing. Genetic testing reveals whether a person has the HD allele, and thus whether he or she will eventually get HD. In order to make an informed decision, people need to have as much knowledge and guidance as possible. The Columbia center’s genetic counselor, Jennifer Williamson-Catania, informs at-risk individuals about the facts of genetic testing and the meaning of HD risk factors. She also makes them aware of reproductive options, such as pre-implantation genetic diagnosis (PGD). (For more information on PGD, click here). Though Ms. Williamson-Catania lays out all of the potential outcomes and alternatives to be considered, she emphasizes that she does not provide any easy “answers” or “solutions.” She is careful not to let her personal values influence the advice she gives, as the decision to be tested is a very serious one, both for the individual and for his or her family. The possibility of a genetic test only further shows how important a full range of support is for families with HD. (For more information on testing, click here).

In Conclusion^

Over the course of their visit, Hou and Tobin were impressed with the devotion and versatility of the center’s team. It was a busy day and the center was sometimes caring for four different patients at once. Yet the team still took the time to patiently answer questions from the HOPES researchers. While Ms. Williamson-Catania showed Hou and Tobin the fMRI room and discussed the difficulties of genetic counseling, she also managed to hurry back to the reception room intermittently to greet patients that had just arrived. Watching the team members in action showed the energy, attention, and empathy they had for their patients. Indeed, the patients had only positive things to say about the care and the sense of community that they experience at the center. It was clear to the HOPES researchers that the Columbia center is a model for the comprehensive care of HD.

-C. Tobin 8-8-06
More

Hennepin County Medical Center of Excellence

In July 2008, HOPES researcher Tiffany Wang visited the Huntington’s Disease Society of America Center of Excellence located at the Hennepin County Medical Center (HCMC) in Minneapolis, Minnesota. The Center of Excellence serves approximately four hundred Huntington’s Disease (HD) patients and families from Minnesota, North Dakota, South Dakota, Northern Iowa and Western Wisconsin. Although it was not formally designated as a Center of Excellence at its start, the HD clinic at HCMC has provided care to HD patients since it was founded in 1978. For more about HDSA Centers of Excellence please click here. Today, under the direction of Medical Director and neurologist Dr. Martha Nance, the HD clinic continues to provide patient care through an expanded program. The clinic is staffed by a multidisciplinary team of specialists, some of whom have worked with the HD clinic for over a decade. HOPES had the opportunity to speak with several of the staff members:

  • Susan Braun-Johnson, P.T. Physical Therapist
  • Sally Gorski, M.A. Speech-Language Pathologist
  • Carol Ludowese, M.S. Genetic Counselor
  • Mary Morgan LaGorio O.T.R. Occupational Therapist
  • Stacey Payerl, R.D. Clinical Dietician
  • Dawn Radtke, R.N. Clinical Research Coordinator
  • Lena Ross, M.S.W. Social Worker
  • David Tupper, Ph.D. Neuropsychologist

Patient Care^

The HCMC Huntington’s Disease clinic is located in the Center’s Neurology department and provides patient care through weekly in-house admittance, monthly HD clinics and visits to long-term care facilities. Some of the clinic’s HD patients represent families that have been with the HCMC clinic for three generations. Generational patient care facilitates strong understanding of patient histories and good patient-physician relations.

Every Wednesday, neurologists Dr. Martha Nance and Dr. Scott Bundlie provide care to HD patients through in-house admittance at the medical center. These appointments with the neurologists are generally for newly diagnosed HD patients, genetic testing consultations and medication changes.

Patients who require other services are advised to visit the clinic during the monthly HD clinic days which occur one Wednesday per month. On these days, a multidisciplinary team of specialists offers services including consultations in neurology, physical therapy, speech-language pathology, genetic counseling, occupational therapy, nutrition, neuropsychology, and social services. Dr. Nance lauds the clinic days as being particularly helpful because patients and their families can see several different physicians and specialists without the hassle of scheduling several appointments or coming to the hospital for multiple visits. HOPES members were able to visit Minneapolis on one of the HD clinic days to see how they are run.

Before the HD clinic opens, the staff holds a meeting to determine the needs of incoming patients. Dr. Nance reviews relevant medical history and highlights concerns that may arise for each of the approximately ten patients who visit on clinic days. By holding the pre-clinic meeting, the staff members are prepared for more meaningful interactions with patients. Following the meeting, the specialists disperse to tend to the patients. Dr. Nance greets most patients personally, inquiring about how the patient has been since his or her last visit. Check-ups for the HD patients are usually scheduled for every three months, so most patients have news to tell Dr. Nance whether it is about serious new symptoms or simply a recent family vacation.

In many instances, the patient’s family and caregivers will accompany them to the clinic and can give insight into how the patient is coping with HD. Family members, particularly siblings and children of HD patients, may want to consider genetic testing. Genetic counselor Carol Ludowese talks with family members about their options for genetic testing. She can also give advice to younger family members about options like pre-implantation genetic diagnosis that would enable them to have children without passing on the genes for HD. For more information about genetic testing click here.

Following each of her consultations, Dr. Nance will report back to the rest of the HD clinic team who will go into the rooms to see the patients. The other specialists will then tailor visits and consultations to the needs of the patients and their families. In addition to finding out how the patients are doing holistically, Dr. Nance also asks more specific questions depending on the condition of the patient. Many of these questions are about topics that can be more thoroughly addressed by one of the specialists on the team.

Dr. Nance often asks about the patient’s weight and eating habits. One of the common symptoms of HD is weight loss, and in the later stages of the disease patients’ weights can fall significantly below healthy levels. If patients are showing drastic weight loss clinical dietician Stacey Payerl offers advice on how to maintain a healthy weight. Her recommendations often extend beyond what kinds of foods to eat to how caregivers can encourage food intake by making eating more enjoyable for the patient.

Speech-language pathologist Sally Gorski can also help patients who are having trouble maintaining a healthy weight. Patients find swallowing becomes more difficult as HD progresses, so she can administer a swallow exam to determine what kinds of foods are safe for a patient to eat without choking. To increase calorie intake and overcome swallowing difficulties, physicians often recommend that a feeding tube be inserted into the stomach. Dr. Nance emphasizes that whether or not a patient wants to have a feeding tube is an important issue to discuss early on because when the time comes to make the decision, the progression of HD may make it too difficult for patients to make the decision or convey their wishes to their families. Gorski can help patients and their families learn more information to help decide whether a feeding tube is right for them. Making the decision to have a feeding tube falls under the category of advanced directives, which Dr. Nance thinks are important to bring up to patients even during beginning stages of the disease.

While engaging the patients and families in conversation, Dr. Nance often asks patients to complete several motor tasks. Some of these actions include sticking the tongue out, walking a short distance, tapping the index and middle fingers against the thumb, and looking in different directions without moving the head. Watching the patients’ performances helps Dr. Nance evaluate which stage of HD they are in according to the Unified Huntington’s Disease Rating Scale (UHDRS). Physical therapist Susan Braun-Johnson and occupational therapist Mary Morgan LaGorio can provide more extensive advice to patients about their physical and motor symptoms, as well as ways to cope with these symptoms. For example, assistive devices can help in daily activity and changes within the home, such as installing additional bathroom equipment, can maximize safety. For more information about assistive devices and physical therapy click here.

Patients are also asked about their mental status and, if they are still formally employed, whether they are experiencing any difficulties at the workplace. These questions can help determine how behavioral and cognitive symptoms are progressing. If more thorough examination is needed, neuropsychologist Dr. David Tupper can administer several neuropsychological tests to determine how a patient’s brain is functioning. Results from these tests not only help members of the HD clinic better understand their patients, but they can also be important for determining qualifications for social security disability.

Questions about disability determination and other topics related to social services can be answered by the social worker Lena Ross on the HD clinic team. She can advise HD patients about resources within the community. One of the recurring topics that Lena receives questions about is health insurance. Given the complex nature of health insurance, patients along with families and caregivers often find it difficult to understand how HD patients can manage their healthcare costs. Lena can also answer questions regarding care for the patients who are progressing into the later stages of HD. Many family members of HD patients find it difficult to balance their busy lives with caring for a loved one with HD. It is important for families to recognize that HD patients can receive meticulous care without becoming a burden for their family at home. If a patient begins showing more severe symptoms, it may be safer to consider other options, such as a long term care facility. In this regard, Lena helps HD families learn about and weigh the options that are available to them.

At the end of the day, the HD clinic team meets again to discuss the status of the patients. Many patients are scheduled for another visit in three months or, if necessary, follow-up visits within a shorter amount of time. Although official reports are documented for each patient, the post-clinic session helps the HD clinic staff familiarize themselves with the patients for more individualized care.

For patients who are in the later stages of HD and cannot go to the clinic in Minneapolis, staff from the clinic visit local long-term care facilities to provide care to HD patients. The HCMC Center of Excellence is affiliated with the Good Samaritan Society – University Specialty Center also located in Minneapolis. The facility provides long-term care to patients with several chronic diseases and has a unit for HD patients that can care for up to fifty patients. Dr. Nance organizes monthly visits to the Good Samaritan Society patients. Whether at the HCMC or the Good Samaritan Society facilities, the HD clinic continues to provide comprehensive and personal care to its patients.

Research^

Dawn Radtke, Clinical Research Coordinator, spoke with HOPES about the research that is conducted at the HCMC Center of Excellence in Minneapolis. The Center has been directly involved with several clinical studies including some drug trials. Although the clinic is not engaged in HD research on the molecular level, the HCMC is affiliated with the University of Minnesota where many groups are researching HD-related biological mechanisms. Several factors are considered when the clinic chooses which studies in which to participate: time involvement for participants and medical staff as well as whether the clinic has an appropriate patient population for the study. Research is mainly focused on relieving the symptoms of HD.

From Ms. Radtke’s experience with patients, families and caregivers are responsive to the idea of participating in clinical trials. Most HD patients are eager to take part in drug studies because receiving a new drug that is not yet FDA approved may alleviate symptoms. Patients are warned, however, that they may receive a placebo rather than the new drug itself.

HCMC researchers face several challenges when conducting clinical trials. Ms. Radtke tells HOPES that the greatest challenge in managing research at the Center of Excellence is time restraints. Some clinical trials require a significant time commitment from participants and all of the studies require time from the medical staff. Another challenge is keeping study participants involved. Although caregivers and family members are usually able to maintain their involvement in studies, it is difficult for HD patients to continue committing to studies as their disease progresses.

The HCMC Center of Excellence has been directly involved with several clinical studies and is currently collecting data for PHAROS, PREDICT-HD, and 2CARE.

PHAROS or the Prospective Huntington At Risk Observational Study monitors individuals who are at risk for HD but have not received genetic testing for the HD allele. By recording characteristics of these participants over time, researchers hope to better understand the progression of HD. At the HCMC Center of Excellence, Dr. Martha Nance is the Primary Investigator and Dr. Scott Bundlie is the independent rater who separately scores participants to ensure that the data is consistent. Ms. Radtke showed HOPES some of the PHAROS tests that are conducted at the HCMC Center of Excellence. Participants are monitored through performance on a verbal fluency test, the Stroop Test, the UHDRS, and questions about frequency and severity of behavioral symptoms.

The PREDICT-HD study is similar to PHAROS, but enrolled subjects are certain that they have the HD allele. The brains of both participants with HD and participants who are at-risk for HD are monitored and compared to better understand the neurological changes associated with HD.

2CARE is a phase III clinical trial investigating the therapeutic effectiveness of the anti-oxidant coenzyme Q10. Enrolled subjects have responded with enthusiasm to this drug trial. To learn more about HD and coenzyme-Q10 click here.

To learn more about clinical trials like the ones conducted at the HCMC and how drugs are developed click here.

Support and Outreach^

The HCMC Center of Excellence works with the Minnesota Chapter of HDSA to offer support for HD families and caregivers. You can visit the HDSA website for the Minnesota Chapter by clicking here. There are monthly support group meetings facilitated by social worker Jessica Hancock. The groups are held in three different regions for the convenience of HD families: the Twin Cities, Northern Minnesota and Northwest Minnesota. In addition to giving HD families an encouraging environment, the support groups will occasionally have guests from the HD clinic to give presentations about health and medical topics. An annual Minnesota HD conference in September gives these groups an opportunity to meet with each other and hear from others who are closely involved with HD, like healthcare workers.

There are also collaborative efforts within the HD community to hold events to raise money for HD. Among these events are an annual Hoop-a-thon started by a local high school basketball player whose mother has HD. The Hoop-a-thon increases HD awareness and raises funds for HD medical research. Events such as the “Hits for Huntington’s” Golf Classic and “Hunt for the Cure” Charity Paintball Big Game also raise money for HD organizations and research.

Several HD families have taken the initiative to reach out to the community and encourage people to learn more about HD. One family whose inspiring story has increased awareness about HD within their community is the Johnson family. The family cares for Mr. Johnson’s childhood friend, Cory Daniels, who was diagnosed with juvenile HD at the age of eighteen, Cory was only given eight months to live when he was put in the care of the Johnsons. HOPES had the opportunity to speak with Mr. Johnson’s wife, Heather, who worked as a registered nurse at a long-term care facility where Cory lived. Heather reconnected the childhood friends who lost touch after high school The Johnsons were aware that community care is more beneficial for patients than institutionalization, so they worked hard to obtain certification so Cory could come to their house to live. Cory has been with the Johnsons for over four years despite physicians’ predictions that he would only live for another eight months. Through organizations like the HCMC center of Excellence and the Minnesota Chapter of HDSA as well as individuals like Cory and the Johnsons, the HD community in Minnesota hopes to continue providing support to one another and increase awareness about HD.

HOPES would like to thank the HDSA Center of Excellence at HCMC and Dr. Nance for allowing us to experience first-hand a clinic that provides quality care to HD patients. We would also like to extend our thanks to Research Coordinator Dawn Radtke for helping to arrange the visit and the Twin Cities Metro Area HD support group members for allowing HOPES to join their July meeting. To visit the website for the HCMC Center of Excellence click here.

- T. Wang, 4/12/2009
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