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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 A型和B型尼曼-匹克病（NPD）是由酸性鞘磷脂酶（ASM）缺乏引起的胆积症。 A型NPD是一种严重的神经病理性疾病，通常会导致三岁以下的死亡。 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被描述过，但没有治疗方法可用于受影响的患者，也没有可靠的生化测试来预测新诊断个体的表型结果。 因此，本提案的具体目的是：1）表征B型疾病中表型的自然史和谱，以预期未来针对该疾病的酶替代疗法（ERT）的临床试验，2）鉴定致病性ASM突变，以及3）鉴定基因型/表型相关性。