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ARRA Investments in Huntington’s disease (HD)


Public Health Burden
HD is a fatal genetic disorder caused by a mutation in a gene called huntingtin (HTT), located on chromosome 4. Patients with HD experience a general lack of coordination and an unsteady gait, a decline in cognitive abilities, and behavioral and psychiatric problems. More than 20,000 people in the United States are diagnosed with HD.  

Understanding and Developing Treatments for HD
There is currently no cure for HD, and life expectancy is generally around 20 years following the onset of symptoms. The development of treatments depends on increasing knowledge of the molecular and cellular events that lead up to and follow the onset of disease symptoms. The following are examples of ARRA projects that are using molecular approaches to develop treatment strategies.
  • Researchers are working on understanding how to block the pathway that leads to the death of cells in the brain in HD. ARRA-funded researchers have found that in mice, loss of a specific enzyme stops DNA damage and delays HD. A follow-up project is testing whether the activity of this enzyme causes the symptoms associated with the disease. 1
  • Research teams are using mouse models to study how different molecules contribute to cell death in HD. One project is studying how blocking a molecule that triggers activation of proteins that cause cells to die may slow the degeneration of neurons.2 Another project is investigating whether the loss of neurotrophic factors, molecules involved in the growth, survival, and maintenance of nerve cells, exacerbates HD symptoms.3 Another is studying whether the elimination of certain proteins can reverse the symptoms of HD.4
  • An ARRA-funded project is using genetic approaches to understand HD pathology in mouse models. This study is designing gene-based therapies for HD by determining whether atypical levels of gene expression correlate with the pathology of HD.5
  • Researchers are characterizing brain atrophy in a mouse model of HD by using magnetic resonance imaging (MRI) - based analysis techniques to measure the location and the time course of neuronal degeneration. This study will also investigate the effect of creatine treatment, a therapy that provides energy to muscles, which has been shown to slow the rate of brain atrophy in HD mouse models. This information will provide insight into how creatine could help Huntington’s patients.6
Research Tools for Developing and Assessing HD Treatments
To develop and test treatments for HD, researchers need valid molecular markers, accurate animal models, and reliable outcome measures. ARRA-funded researchers are creating the following tools that will potentially help the HD research community to develop treatments, and to assess the efficacy of these treatments.
  • A GO grant recipient has formed a consortium to develop and characterize induced pluripotent stem (iPS) cells, stem cells created from the skin of HD patients. This group will distribute neural stem cells derived from HD and normal iPS cell lines to members of the consortium, and generate a panel of models of the mutation that causes HD in order to assist researchers studying the underlying biology of HD, and to aid in drug discovery.  7
  • Researchers are creating a mouse model that more accurately replicates the molecular pathology of HD in humans, by increasing the repeat length of the HD mutation, and therefore increasing the severity of the disease in mice. Having mouse models with varying severity of HD will be a valuable resource to researchers interested in testing potential drugs. 8
  • An ARRA-funded project is developing sensitive and meaningful outcome measures of health-related quality of life (HRQOL) in persons with HD. A measure like this will be used alongside measures of physical functioning, emotional functioning, and adverse events (such as the United Huntington's Disease Rating Scale) as an outcome measure for clinical trials in HD. 9
  • Although HD patients are born with the mutation in HTT, physical symptoms usually emerge after the age of 35. The PREDICT-HD study, an international 32-site observational study of persons at-risk for HD, will help define the neurobiology of HD before individuals have diagnosable symptoms. This will allow researchers to conduct clinical trials at earlier stages of the disease. ARRA funds will supplement this ongoing study by providing resources to collect biological specimens from patients,10 create new cell lines,11 and capture data electronically.12    



  1. 1R01NS062384-01A2 -- Age of Onset and Huntingtons Disease- McMurray, Cynthia Therese
  2. 3R01NS051756-04S1 -- Identification of Novel Drugs that Counter Huntington's Disease -- Friedlander, Robert M. (MA)
  3. 1R01NS059936-01A1 -- Huntington's Disease and the Striatum- Ehrlich, Michelle E.
  4. 2R01NS050199-06 -- Protein Trafficking in Neurodegenerative Diseases -- Yamamoto, Ai (NY)
  5. 1R01NS067458-01 -- Dysregulation of MicroRNAs in Huntington’s Disease -- Friedlander, Robert M.(MA)
  6. 1R21NS065306-01 -- Characterization of brain atrophy in Huntington’s disease mouse model-- Zhang, Jiangyang (MD)
  7. 1RC2NS069422-01 -- The Huntington's Disease iPS Consortium- Finkbeiner, Steven M; Gusella, James F; Ross, Christopher A; Svendsen, Clive Niels; Thompson, Leslie Michels (Contact) (CA)
  8. 3R21NS059647-02S1 -- Mice for development of HD therapeutics-- Detloff, Peter J. (AL)
  9. 1R03NS065194-01 -- Health-Related Quality of Life in Huntington’s Disease Research and Practice: Carlozzi, Noelle E. (NJ)
  10. 3R01NS040068-09S1 -- Neurobiological Predictors of Huntington's Disease-- Paulsen, Jane S (IA)
  11. 3R01NS040068-09S2 -- Neurobiological Predictors of Huntington's Disease-- Paulsen, Jane S (IA)
  12. 3R01NS040068-09S3 -- Neurobiological Predictors of Huntington's Disease-- Paulsen, Jane S (IA)


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