NIEMANN-PICK DISEASE: GENOTYPE/PHENOTYPE ANALYSES AND MOLECULAR BASED THERAPY

尼曼匹克病：基因型/表型分析和分子治疗

• 批准号: 7718115
• 负责人: MARGARET M MCGOVERN
• 金额: $ 5.14万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718115
• 关键词: Adolescence; Affect; Age-Years; Biochemical; Cessation of life; Classical Niemann-Pick Disease; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Future; Genotype; Grant; Individual; Institution; Molecular; Mutation; Natural History; Neurologic; Newly Diagnosed; Niemann-Pick Diseases; Non-Neuronopathic Type Niemann-Pick Disease; Outcome; Patients; Phenotype; Research; Research Personnel; Resources; Source; Testing; United States National Institutes of Health; acid sphingomyelinase; base; enzyme replacement therapy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Types A and B Niemann-Pick disease (NPD) are storage disorders resulting from the deficiency of acid sphingomyelinase (ASM). Type A NPD is a severe neuronopathic disorder which uniformly leads to death by three years of age. In contrast, patients with Type B NPD have little or no neurologic involvement and often survive into late adolescence or adulthood. Despite the fact that this disorder was described over seventy years ago, no treatment is available for affected patients and no reliable biochemical tests have been developed to predict the phenotypic outcome of newly diagnosed individuals. Thus, the specific aims of this proposal are to: 1) characterize the natural history and spectrum of the phenotype in Type B disease in anticipation of a future clinical trial of enzyme replacement therapy (ERT) for this disorder, 2) identify causative ASM mutations, and 3) identify genotype/phenotype correlations.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 A 型和 B 型尼曼-匹克病 (NPD) 是由于酸性鞘磷脂酶 (ASM) 缺乏而导致的贮积病。 A 型 NPD 是一种严重的神经病性疾病，通常会导致三岁时死亡。 相比之下，B 型 NPD 患者很少或没有神经系统受累，并且通常能存活到青春期后期或成年期。 尽管这种疾病在七十多年前就已被描述，但受影响的患者尚无可用的治疗方法，也没有开发出可靠的生化测试来预测新诊断个体的表型结果。 因此，该提案的具体目标是：1) 描述 B 型疾病表型的自然史和谱，以预测未来对该疾病的酶替代疗法 (ERT) 的临床试验，2) 识别致病的 ASM 突变和 3) 确定基因型/表型相关性。