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 Sjgren-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.

Public Health Relevance

The diseases studied by STAIR often go undiagnosed and have puzzling symptoms. Even after diagnosis, they have no effective therapies, leaving patients and families frustrated and disheartened. The STAIR Consortium will uncover highly relevant knowledge that is likely to advance considerably the diagnosis and therapeutic options for patients with these rare diseases.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54HD061939-06
Application #
8765237
Study Section
Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Krotoski, Danuta
Project Start
2009-07-01
Project End
2019-08-31
Budget Start
2014-09-04
Budget End
2015-08-31
Support Year
6
Fiscal Year
2014
Total Cost
$900,000
Indirect Cost
$203,362
Name
University of Nebraska Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Merkens, Mark J; Sinden, Nancy L; Brown, Christine D et al. (2014) Feeding impairments associated with plasma sterols in Smith-Lemli-Opitz syndrome. J Pediatr 165:836-41.e1
DeBarber, Andrea E; Luo, Jenny; Star-Weinstock, Michal et al. (2014) A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J Lipid Res 55:146-54
DeBarber, Andrea E; Luo, Jenny; Giugliani, Roberto et al. (2014) A useful multi-analyte blood test for cerebrotendinous xanthomatosis. Clin Biochem 47:860-3
He, Miao; Smith, Laurie D; Chang, Richard et al. (2014) The role of sterol-C4-methyl oxidase in epidermal biology. Biochim Biophys Acta 1841:331-5
Liu, Wei; Xu, Libin; Lamberson, Connor R et al. (2013) Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients. J Lipid Res 54:244-53
Kanungo, Shibani; Soares, Neelkamal; He, Miao et al. (2013) Sterol metabolism disorders and neurodevelopment-an update. Dev Disabil Res Rev 17:197-210
Simon, Anna; Drenth, Joost P H; Matern, Dietrich et al. (2013) Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable periodic fevers. Mol Genet Metab 108:166-71
Hager, Elizabeth J; Piganelli, Jon D; Tse, Hubert M et al. (2012) Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS). J Inherit Metab Dis 35:159-68
DeBarber, Andrea E; Eroglu, Yasemen; Merkens, Louise S et al. (2011) Smith-Lemli-Opitz syndrome. Expert Rev Mol Med 13:e24
Monson, Dinelli M; DeBarber, Andrea E; Bock, Charles J et al. (2011) Cerebrotendinous xanthomatosis: a treatable disease with juvenile cataracts as a presenting sign. Arch Ophthalmol 129:1087-8

Showing the most recent 10 out of 13 publications