Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, dementia and personality disorder affecting between 5 to 10 persons per 100,000 in the U.S. Although the mean age of onset of HD is about 40 years of age, manifestations of the disease may occur as early as 2 and later than 80 years of age. There is no effective treatment for HD which is progressive and follows an inexorable course leading first to total debilitation and then death some 15 to 20 years after onset. Typically the HD patient requires several years of full time nursing care and the disease can represent an extraordinary psychological and financial burden for both their family and society as a whole. The Huntington's Disease Center Without Walls is a basic research center that was established in 1980 with clearly stated goals: the discovery of the nature of the genetic defect causing HD, the elucidation of the mechanisms whereby this defect acts to produce the clinical and pathologic features of the disorder, and the development of effective approaches to its treatment. The Center is multidisciplinary, encompassing in a single cooperative program a broad range of research approaches including genetics, epidemiology, biochemistry, and neuroanatomy. In the past grant cycle we accomplished the goal of identifying the HD mutation. The disorder is caused by an expanded, unstable CAG trinucleotide repeat in a gene encoding a large novel protein named huntington. In this renewal period we intend to study the dynamic behavior of the HD CAG repeat, its clinical correlates, factors that modify these parameters, the origin of repeat instability, the connection between CDA expansion and impairment of energy metabolism, the consequences of CAG expansion on neural development and anatomy, on structure, expression, localization and interactions of huntingtin protein and on metabolism of cultured neuronal cells. The HD Center comprises a team of highly interactive investigators with a unique combination of talents and considerable experience and dedication to HD. We are confident that the next 5 years will see tremendous strides toward achieving our goals of understanding the nature and consequences of the genetic defect, and of being able to provide an effective treatment for this devastating disorder.
Showing the most recent 10 out of 42 publications
