R01NS114562

Understanding the contribution of altered cerebrovascular function to the pathology and clinical symptoms of Huntington disease - Project Summary/Abstract: This proposal seeks to establish the pathophysiological mechanisms that establish a relationship between neurovascular dysfunction, neurological impairment, and brain degeneration in Huntington's disease (HD). It builds on our growing understanding of the importance of neurovascular alterations in neurodegeneration, including in HD, and takes advantage of clinical and neuroimaging expertise as well as the availability of a well-characterized cohort of HD gene-expanded individuals.

Aim 1 examines the cross-sectional regional changes in cerebrovascular reactivity (CVR) and tests the hypothesis that impaired CVR triggers focal brain atrophy. Aim 2 tests the specific hypothesis that impaired perfusion (CBF) occurs in HD and is associated with regionally altered CVR. Aim 3 evaluates the longitudinal neurovascular changes and the causal relationship between location and severity of these changes with rates of clinical progression and of brain atrophy.

Successful achievement of these aims will establish a strong foundation for understanding key vascular mechanisms that may affect progression and HD and establish neurovascular mechanisms as important targets for future clinical drug trials in HD.

The General Hospital Corporation

NOT APPLICABLE

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Charlestown, Massachusetts 02129 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the End Date has been extended from 11/30/25 to 05/31/27 and the total obligations have increased 387% from $683,656 to $3,331,153.