Clinical progression and pathologic correlates of Huntington's disease

亨廷顿病的临床进展和病理相关性

• 批准号: 8129438
• 负责人: Adam Rosenblatt
• 金额: $ 23.52万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8129438
• 关键词: Biochemical; Cell Death; Cell model; Cells; Clinical; Clinical Research; Epidemiology; Examinations and Diagnoses; Family; Functional Imaging; Functional disorder; Genes; Genetic screening method; Goals; Huntington Disease; Individual; Measurement; Molecular; Pathogenesis; Pathologic; Pathway interactions; Patients; Phenotype; Proteins; Research; Sampling; Testing; Therapeutic Intervention; Tissues; Transgenic Mice; cerebral atrophy; follow-up; genetic manipulation; genetic variant; human Huntingtin protein; interest; mouse model; novel therapeutic intervention; programs

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.

这是亨廷顿病从分子到临床研究的综合项目。一个项目涉及对来自流行病学样本的一组特征明确的家庭的 HD 患者和相关表型患者进行纵向临床研究。 第二个项目使用结构和功能成像来纵向测量脑萎缩和功能障碍，特别关注早期 HD 和症状前基因阳性个体。 第三个项目涉及 HD 发病机制的生化和细胞生物学研究，重点关注亨廷顿蛋白的潜在蛋白水解裂解、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途径并开发治疗干预措施。 第四个项目将利用我们的 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。 一个核心提供管理和统计支持。 第二个核心提供患者的检查、诊断和纵向随访。 第三个核心提供神经病理学检查、诊断和研究用组织。 第四个核心提供基因测试和鉴定有助于表型的遗传变异。 总体而言，该项目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。