Clinical progression and pathologic correlates of Huntington's disease

这是一个从分子到临床的亨廷顿病研究的综合项目。一个项目涉及对HD患者和相关表型的纵向临床研究，这些患者来自一组特征良好的家系，这些家系来自流行病学样本。第二个项目使用结构和功能成像对大脑萎缩和功能障碍进行纵向测量，特别关注早期HD和症状前基因阳性的个体。第三个项目涉及HD发病机制的生化和细胞生物学研究，重点是亨廷顿蛋白潜在的蛋白水解性切割，亨廷顿蛋白相关蛋白的可能参与，以及使用细胞模型来了解细胞死亡的途径和开发治疗干预措施。第四个项目将使用我们的HD转基因小鼠模型的药理学和遗传操作来确定改善表型的可能方法。这些项目由四个核心支持。一个核心提供行政和统计支助。第二个核心提供对患者的检查、诊断和纵向跟踪。第三个核心提供神经病理检查、诊断和研究组织。第四个核心是对影响表型的基因变异进行基因测试和鉴定。总体而言，该计划的目标是更好地了解HD的分子和细胞发病机制，并开发和测试新的治疗方法。

This is an integrative program of Huntington's disease research ranging from the molecular to the clinical. One project involves a longitudinal clinical study of patients with HD and related phenotypes from a set of well characterized families deriving from an epidemiologic sample. A second project uses structural and functional imaging for longitudinal measurement of cerebral atrophy and dysfunction with a special interest in early HD and pre-symptomatic gene positive individuals. A third project involves biochemical and cell biologic studies of the pathogenesis of HD, focusing on the potential proteolytic cleavage of huntingtin, the possible involvement of huntingtin associated proteins, and the use of cell models to understand pathways of cell death and develop therapeutic interventions. A fourth project will use pharmacologic and genetic manipulations of our HD transgenic mouse model to determine possible means of ameliorating the phenotype. These projects are supported by four cores. One core provides administrative and statistical support. A second core provides examination, diagnosis and longitudinal follow up of patients. A third core provides neuropathologic examination, diagnosis, and tissue for research. A forth core provides genetic testing and identification of genetic variants which contribute to phenotypes. Overall, the goal of the program is to better understand the molecular and cellular pathogenesis of HD, and develop and test new therapeutic approaches.