Sterol and Isoprenoid Diseases Consortium

University Of Nebraska Medical Center, Omaha NE

Investigators

Linked publications & trials

Abstract

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.