Arches. Photo by Daniel Chia
Jun
26
2010

More Research Institutions

Readers of our website sometimes ask, “Where does all the research summarized by HOPES come from?” Here follows a list of some main contributors to HD research, along with some of their recent studies, clustered in five categories:

We’ve also included some news articles highlighting the key discoveries. You will notice that the “Recommended Reading” list at the end draws directly from medical journals, so please be forewarned: the material there may be complex.

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Biological Basis of HD^

Johns Hopkins University School of Medicine
http://www.hopkinsmedicine.org/psychiatry/specialty_areas/huntingtons_disease/index.html
Director: Christopher A. Ross, M.D., Ph.D.

  • Discovered a gene that, when mutated, causes a disorder called “Huntington’s disease-like 2,” or HDL2, which is very similar to HD.
  • Found a way to make the CREB binding protein (a protein involved in the neuronal effects of HD) harmless by cutting out certain molecular areas.
  • Determined that HD causes movement abnormalities by preventing the basal ganglia in the brain from correcting its mistakes.

Representative News Articles:
http://www.jhu.edu/~gazette/2002/28oct02/28novel.html
http://www.hopkinsmedicine.org/press/2002/August/020806.htm

University of California, Irvine

  • Found that a certain protein called arfaptin 2 can prevent the huntingtin protein from aggregating, although it is still unclear whether or not these aggregates cause HD.
  • Discovered that a class of drugs called “histone deacetylase inhibitors” can actually prevent, and in some cases reverse, brain cell death in fruit flies.

Representative News Article:
http://today.uci.edu/news/release_detail.asp?key=519

Weill College of Medicine at Cornell University

  • Used metabolism studies to show that mice who have the HD allele do not use energy as efficiently as normal mice do.

University of Pennsylvania School of Medicine

  • Used fruit flies to show that certain protein chaperones may suppress HD.
  • First to discover that HD causes proteins to aggregate in the brain.

Stanford University

  • Found that huntingtin aggregates cause proteasomes to malfunction, which creates problems when toxic proteins collect.
  • For more information about research at Stanford, click here.

Mayo Clinic

  • Researched why mutant proteins cannot be degraded in patients with HD.

HD Genetics^

Indiana University School of Medicine

  • Sends researchers to Lake Maracaibo, Venezuela, a community that has a high number of related individuals who are predisposed to developing HD. Researchers obtain specimen samples and test neurological functions to determine the genetic inheritance of HD.

University of Southern California

  • Studied the Lake Maracaibo community and found that HD is caused by many genetic mutations that happen during mitosis—not just one in meiosis—and that the number of CAG repeats on the HD allele increases as the mutations accumulate over time.

Massachusetts General Hospital

  • Found that certain types of brain cells tend to appear in higher densities in people who have a family history of HD.
  • Studied the effects of HD on the transcription of genes across generations.

The Search for Treatments^

Massachusetts General Hospital

  • Tested coenzyme Q10 as a potential treatment for HD, and found that the drug can extend patients’ lives and delay the onset of symptoms.
  • Performed an inconclusive clinical trial of riluzole, a drug that had been shown to improve motor abnormalities in HD-afflicted baboons. Investigations of riluzole continue.

National Institutes of Aging (NIA)

  • Recently found that periods of fasting decreased the symptoms of HD in mice. Low-calorie diets and reduced meal frequency can both delay the onset of HD and slow down the spread of the disease.

Representative article:
http://www.sciencedaily.com/releases/2003/02/030211072836.htm

University of South Florida Center for Aging and Brain Repair

  • Found that people whose diets are rich in antioxidants age slower because antioxidants block the free radicals that cause body function to decline.
  • Successfully slowed aging in the brain by implanting stem cells from human umbilical cord blood.
  • Discovered that when fetal tissue is implanted in the brains of HD patients, the new tissue remains free of HD.

Representative articles:
http://www.mcleanhospital.org/PublicAffairs/20001130_huntingtons.htm
http://www.cnn.com/2001/fyi/news/08/09/fetal.cell/

Stanford University

  • Challenged the relationship between protein aggregates and HD with the discovery that drugs such as cystamine can reduce the symptoms of HD without affecting aggregates.

Weill College of Medicine at Cornell University

  • Conducted key research on potential HD treatments such as coenzyme Q10 and creatine.

Psychological Studies^

Columbia Health Science HDSA Center for Excellence at the New York State Psychiatric Institute

  • Found that HD patients’ grasping abilities decrease more and more over time.
  • Studied a group of HD patients and found that over half of them had symptoms of obsessive-compulsive disorder.
  • Currently exploring the safety of creatine for the treatment of HD.

Indiana University School of Medicine

  • Recruited patients with a family history of HD and found that the ones who eventually developed the disease became more irritable and hostile before any other signs of HD appeared.

Johns Hopkins University School of Medicine

  • Most HD patients also suffer from depression, impaired thinking, personality changes, and other disorders that can be treated with medication.

Representative Article:
http://www.hopkinsmedicine.org/press/2000/FEBRUARY/000203.HTM

University of Connecticut Medical School

  • Found that when HD patients are asked to do a cognitive task (like solving a word puzzle, for instance), less blood flows through their brains than through the brains of people who don’t have the disease.

University of Pennsylvania School of Medicine

  • Found that HD patients are less able to identify odors than people who do not have HD.

Link to Publication:
http://www.med.upenn.edu/stc/papers/1997/97byla.pdf

Clinical Trials^

Huntington Study Group (HSG)
HSG is a worldwide collaboration of researchers and physicians who work together to study HD. The group has produced numerous studies in the past; current projects include:

  • MINO-HD: Aims to determine exactly how the drug minocycline affects HD patients. There is already evidence suggesting that the drug has positive effects, since minocycline prevents the expression of caspase, an enzyme that triggers certain events that lead to cell death.
  • Prospective Huntington At Risk Observational Study (PHAROS): Plans to monitor people who are genetically at-risk for developing HD and to try and determine the circumstances under which these people actually go on to develop the disease.
  • PREDICT-HD: Compares the brains of HD patients with those who are “at-risk” for HD to find out what triggers the disease. The difference between this study and PHAROS is that PREDICT-HD is recruiting patients who already know that they have the HD allele, whereas volunteers for PHAROS cannot know whether or not they have the mutation.

University of Rochester School of Medicine and Dentistry

  • Researched the rate at which HD patients’ motor skills decline.
  • Developed a method to test the reliability of diagnosing HD.

For Further Reading:

  1. Albin RL. Fetal striatal transplantation in Huntington’s disease: time for a pause. Journal of Neurology, Neurosurgery, Psychiatry. 2002 Dec; 73(6):612.
  2. Bonini NM. Chaperoning brain degradation. Proceedings of the National Academy of Sciences. Dec 10;99 Suppl 4:16407-11.
  3. Cattaneo E, Rigamonti D, Zuccato C. The enigma of Huntington’s disease. Scientific American. 2002 Dec; 287(6): 92-7.
  4. Kieburtz K. Issues in transplantation for Huntington’s disease. Cell Transplantation. 1999 July/Aug;8:456-457.
  5. McMurray CT. Huntington’s disease: new hope for therapeutics. Trends in Neuroscience. 2001 Nov;24(11 Suppl):S32-8.
  6. Parker M, Lucassen A. Working towards ethical management of genetic testing. Lancet. 2002 Nov 23;360(9346):1685-8.
  7. Sharma N, Standaert DG. Inherited movement disorders. Neurological Clinician. 2002 Aug;20(3): 759-78.

-G. Schiel 5-01-03