The Baltimore Huntington's Disease Project (BHDP) is a cohesive research program, which includes research on etiology, pathogenesis, and treatment. In this application, we request funding for years 11-15. Using a variety of new methods, we propose to study the mechanism of gene action in HD. Dr. Orest Hurko (Mitochondrial Function) approaches the question through Dr. Joseph Coyle (Selective Neuronal Vulnerability) uses the rodent HD model and neuronal culture to investigate the basic mechanisms leading to glutamate-induced excitotoxicity and will test drugs in these systems for their ability to prevent neuronal damage. One outcome of this work is a separately funded Experimental Therapeutic Trial of Idebenone. A related theme is the role of extra-striatal pathology in HD. Drs. Chris Ross and John Hedreen (Extra-Striatal Pathology) use neuropathological and neurochemical experiments to elucidate the pathogenetic meaning of cortical and amygdala pathology in HD. Dr. Jason Brandt (Correlates of Frontal- Striatal Degeneration) uses neuropsychological methods to assess the significance of cortical atrophy (using MRI) in cognitive and functional deficits. Dr. David Zee (Ocular Motor Function), uses novel paradigms for testing ocular motor function in HD patients to study the anatomy and function of ocular motor pathways and their changes in HD. The BHDP is coordinated through its Cores, and through the physical proximity of the investigators whose offices and laboratories are in the Meyer Building. The Administrative Core provides both formal and informal forums for discussion of ideas and progress, and provides statistical services for all Projects and Cores. The Clinical Core recruits and maintains approximately 300 well-characterized HD patients. A separately funded research project, Presymptomatic Testing for HD, grew out of the resources of the Clinical Core. The Pathology Core has brain material on over 70 HD patients, most of whom were followed until death by the Clinical Core. Progress will be reviewed by an External Review Committee. Our in-house Ethics Committee reviews questions relating to patient participation in research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS016375-15
Application #
2263005
Study Section
Special Emphasis Panel (SRC (04))
Project Start
1980-07-01
Project End
1996-04-18
Budget Start
1994-12-01
Budget End
1996-04-18
Support Year
15
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wu, Dan; Faria, Andreia V; Younes, Laurent et al. (2017) Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease. Hum Brain Mapp 38:5035-5050
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
Younes, Laurent; Ratnanather, J Tilak; Brown, Timothy et al. (2014) Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis. Hum Brain Mapp 35:792-809
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

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