Sterol and Isoprenoid Diseases Consortium

甾醇和类异戊二烯疾病联盟

• 批准号: 9348659
• 负责人: WILLIAM B. RIZZO
• 金额: $ 60万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9348659
• 关键词: Abbreviations; Applications Grants; Behavioral; Bile Acids; Biochemical Pathway; Biological Markers; Canada; Cholesterol; Clinical; Clinical Research; Clinical Skills; Combined Modality Therapy; Defect; Diagnosis; Dietary Cholesterol; Disease; Disease Progression; Dolichol; Family; Feasibility Studies; Fever; Funding; Genes; Geographic Distribution; Inherited; International; Intervention Studies; Investigation; Knowledge; Laboratories; Lead; Life; Magnetic Resonance Imaging; Medical; Metabolic; Metabolic Diseases; Mevalonate kinase; Mission; Monitor; Mutation; Natural History; Nature; Netherlands; Outcome Measure; Pathogenesis; Pathogenicity; Pathway interactions; Patient Recruitments; Patients; Periodicity; Phenotype; Physicians; Pilot Projects; Rare Diseases; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resource Sharing; Scientist; Side; Site; Sitosterols; Sjogren-Larsson Syndrome; Smith-Lemli-Opitz Syndrome; Sterols; Supplementation; Symptoms; Therapeutic; Therapeutic Intervention; Therapeutic Trials; Training; Training Support; Treatment Efficacy; Variant; Work; cholesterol biosynthesis; data management; disease-causing mutation; effective therapy; experience; gene synthesis; innovation; isoprenoid; member; mevalonate; next generation; patient advocacy group; patient population; public health relevance; research study

DESCRIPTION (provided by applicant): The Sterol and Isoprenoid Diseases Research Consortium (STAIR) is dedicated to the investigation of rare inherited metabolic diseases that are caused by genetic defects in the biochemical pathway leading to the synthesis of sterols, isoprenoid-related molecules and metabolic products of cholesterol, such as bile acids. The objectives of the Consortium are to define the natural history and phenotypic variation of STAIR diseases, identify biomarkers that are useful as surrogate clinical outcome measures, elucidate disease pathogenesis and develop effective therapeutic interventions. The Consortium team consists of 1) clinician scientist leaders in the field, several having first discovered the geneti basis for STAIR diseases, 2) Patient Advocacy Groups to aid clinical study feasibility, recruitment and implementation and 3) the Data Management Coordinating Center (DMCC) to provide statistical support. STAIR Consortium sites are located throughout the US, Canada and the Netherlands. STAIR sites are selected to provide a wide geographic distribution and take advantage of available rare patient populations. We will accomplish STAIR objectives by performing collaborative multicenter clinical research studies and short pilot projects. Longitudinal natural history studies will focus on Sjögren-Larsson syndrome, Hyper-lgD/mevalonate kinase deficiency with periodic fevers, and newly recognized Dolichol Synthesis defects. An ongoing interventional study will examine the effect of dietary cholesterol supplementation in Smith-Lemli-Opitz syndrome. The behavioral/MRI abnormalities of subjects who are heterozygous carriers for deleterious cholesterol synthesis genes will be investigated. A pilot study will determine the optimal combination therapy for patients with Sitosterolemia. In conjunction with its clinical mission, STAIR will support the training of at least 2 new young investigators to develop the necessary laboratory and clinical skills to become leaders in rare disease research. In summary, the work of the STAIR Consortium over the next 5 years will have major impact on the understanding of the natural history, phenotypic variation and potential therapy of these rare diseases.

描述（由申请人提供）：固醇和类异戊二烯疾病研究联盟（STAIR）致力于研究罕见的遗传性代谢疾病，这些疾病是由导致固醇、类异戊二烯相关分子和胆固醇代谢产物（如胆汁酸）合成的生化途径中的遗传缺陷引起的。该联盟的目标是确定STAIR疾病的自然史和表型变异，确定可用作替代临床结局指标的生物标志物，阐明疾病发病机制并开发有效的治疗干预措施。该联盟团队由1）该领域的临床科学家领导者组成，其中一些人首先发现了STAIR疾病的遗传基础，2）患者倡导小组，以帮助临床研究的可行性，招募和实施，以及3）数据管理协调中心（DMCC）提供统计支持。STAIR Consortium的网站遍布美国、加拿大和荷兰。选择STAIR研究中心以提供广泛的地理分布并利用可用的罕见患者人群。我们将通过开展合作性多中心临床研究和短期试点项目来实现STAIR的目标。纵向自然史研究将集中在Sjöling-Larsson综合征，Hyper-lgD/甲羟戊酸激酶缺乏症伴周期性发热，以及新发现的Dolichol合成缺陷。一项正在进行的干预性研究将检查饮食胆固醇补充剂对Smith-Lemli-Opitz综合征的影响。将研究有害胆固醇合成基因杂合子携带者受试者的行为/MRI异常。一项初步研究将确定谷甾醇血症患者的最佳联合治疗。结合其临床使命，STAIR将支持培训至少2名新的年轻研究人员，以发展必要的实验室和临床技能，成为罕见疾病研究的领导者。总之，STAIR联盟未来5年的工作将对理解这些罕见疾病的自然史、表型变异和潜在治疗产生重大影响。