Sterol and Isoprenoid Diseases Consortium

描述(由申请人提供)：斯特罗和异戊二烯类疾病研究联盟(STAIR)致力于研究罕见的遗传性代谢性疾病，这些疾病是由导致类固醇、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。该联盟的目标是定义楼梯疾病的自然历史和表型变异，识别可用作替代临床结果衡量标准的生物标记物，阐明疾病的发病机制，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，其中几人首先发现了楼梯疾病的Geneti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)，以提供统计支持。Stair Consortium的生产基地遍布美国、加拿大和荷兰。选择楼梯位置是为了提供广泛的地理分布，并利用可用的稀有患者群体。我们将通过进行协作的多中心临床研究和短期试点项目来实现阶梯目标。纵向自然病史研究将集中在Sjögren-Larsson综合征、伴有周期性发烧的高LGD/甲氧戊酸激酶缺乏症以及新发现的多醇合成缺陷。一项正在进行的干预性研究将检验膳食胆固醇补充对Smith-Lemli-Opitz综合征的影响。有害胆固醇合成基因杂合子携带者的行为/核磁共振异常将被调查。一项先导性研究将确定西托类固醇血症患者的最佳联合疗法。结合其临床任务，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。总而言之，STRIR协会在未来5年的工作将对理解这些罕见疾病的自然历史、表型变异和潜在的治疗方法产生重大影响。

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.