Sterol and Isoprenoid Diseases Consortium

甾醇和类异戊二烯疾病联盟

基本信息

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
项目类别：
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

项目摘要

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）：甾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，这些疾病是由导致甾醇、类异戊二烯相关分子合成和代谢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，识别可用作替代的生物标志物。该联盟团队由 1) 该领域的临床科学家领导者组成，其中几位首先发现了 STAIR 疾病的遗传基础，2) 帮助临床研究可行性和招募的患者倡导小组。 3) 数据管理协调中心（DMCC）提供统计支持 STAIR 联盟站点分布在美国、加拿大和荷兰，以提供广泛的地理分布和利用。我们将通过开展协作性多中心临床研究和短期试点项目来实现 STAIR 目标，该研究将重点关注干燥综合征、高 lgD/甲羟戊酸激酶缺乏症和新发现的多利醇。一项正在进行的干预性研究将检查膳食胆固醇补充剂对史密斯-莱姆利-奥皮茨综合征杂合子携带者的行为/MRI 异常的影响。一项试点研究将研究有害的胆固醇合成基因，以确定谷甾醇血症患者的最佳联合疗法，同时 STAIR 将支持培训至少 2 名新的年轻研究人员，以培养必要的实验室和临床技能。总之，STAIR 联盟未来 5 年的工作将对这些罕见疾病的自然史、表型变异和潜在治疗的理解产生重大影响。