Abstract

The overall goal of this project is to facilitate the discovery and implementation of rational therapy for HD by careful analysis of the unique clinical data generated in the Clinical Core, defining the determinants of the course of HD. This will be accomplished by examining three different sets of hypotheses.
In Specific Aim 1, we will test the hypothesis that CAG repeat number and other variables can be used to develop accurate models of the onset and course of HD. We hypothesize that CAG repeat length has a small but significant influence on the rate of disease progression. We will also test the hypothesis that familial factors in addition to CAG repeat length affect the course of HD.
In Specific Aim 2, we will characterize neuropsychological features of early HD, and correlates of clinical and brain abnormalities.
In Specific Aim 3, we will use a novel robotic system for defining the progressive motor disorder in HD expansion positive individuals and HD patients.
In Specific Aim 4, we will test the hypothesis that diseases similar to HD are also caused by CAG expansion mutations. We will identify the genetic etiology of one of these diseases. In summary, we will provide new approaches for understanding HD?s clinical course, which will provide clues to pathogenesis and the development of novel treatment strategies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS016375-21A1
Application #
6465792
Study Section
Project Start
1980-07-01
Project End
2006-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
21
Fiscal Year
2001
Total Cost
$172,411
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Faria, Andreia V; Ratnanather, J Tilak; Tward, Daniel J et al. (2016) Linking white matter and deep gray matter alterations in premanifest Huntington disease. Neuroimage Clin 11:450-460
Krause, Amanda; Mitchell, Claire; Essop, Fahmida et al. (2015) Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am J Med Genet B Neuropsychiatr Genet 168:573-85
Ross, Christopher A; Pantelyat, Alex; Kogan, Jane et al. (2014) Determinants of functional disability in Huntington's disease: role of cognitive and motor dysfunction. Mov Disord 29:1351-8
Hua, Jun; Unschuld, Paul G; Margolis, Russell L et al. (2014) Elevated arteriolar cerebral blood volume in prodromal Huntington's disease. Mov Disord 29:396-401
Unschuld, Paul G; Liu, Xinyang; Shanahan, Megan et al. (2013) Prefrontal executive function associated coupling relates to Huntington's disease stage. Cortex 49:2661-73
Biglan, K M; Dorsey, E R; Evans, R V V et al. (2012) Plasma 8-hydroxy-2'-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10. J Huntingtons Dis 1:65-9
Unschuld, Paul G; Joel, Suresh E; Liu, Xinyang et al. (2012) Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease. Neurosci Lett 514:204-9
Unschuld, Paul G; Joel, Suresh E; Pekar, James J et al. (2012) Depressive symptoms in prodromal Huntington's Disease correlate with Stroop-interference related functional connectivity in the ventromedial prefrontal cortex. Psychiatry Res 203:166-74
Aggarwal, Manisha; Duan, Wenzhen; Hou, Zhipeng et al. (2012) Spatiotemporal mapping of brain atrophy in mouse models of Huntington's disease using longitudinal in vivo magnetic resonance imaging. Neuroimage 60:2086-95
Lee, Youngjin; Morrison, Brett M; Li, Yun et al. (2012) Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487:443-8

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