NINDS Biomarkers in Multiple Sclerosis Study (BioMS)

To identify biomarkers (by gene- and protein expression profiling, single nucleotide polymorphism (SNP) haplotype determination, HLA typing) and link these with clinical- and MRI phenotypes in a large cohort of relapsing-remitting (RR-) MS patients. To identify biomarkers that separate MS patients and healthy, matched controls.

STUDY POPULATION: Up to 1000 patients who are enrolled in and treated under a multi-center trial of combination therapy (MS-CombiRx) using two approved disease-modifying therapies (interferon-beta, IFN-b, Avonex; glatiramer-acetate, GA) as single treatments or in combination. 200 healthy, matched control individuals.

DESIGN: Samples of serum and white blood cells will be obtained on each patient prior to randomization in the MS-CombiRx study and then at 6 months 1, and 3 years following randomization. Samples will be analyzed for SNP haplotype, gene and protein expression, and HLA haplotype. Samples from controls will be analyzed in the same fashion, however, only one time point will be analyzed, and there will be no treatment of controls.

OUTCOME MEASURES: The results of the biomarker studies will be assessed in relationship to both the clinical and MRI phenotype at baseline and to change in disability, relapse rate, response to therapy and change in MRI measures of disease during the 3-year treatment period. Each of the biomarker study components will be analyzed with respect to biomarkers that discriminate between MS patients and controls.

SIGNIFICANCE: Similar to rheumatoid arthritis or autoimmune diabetes multiple sclerosis (MS) is considered a complex disease with autoimmune pathogenesis as well as vulnerability of the target tissue, i.e. the central nervous system (CNS). The results of the biomarker study should provide a better understanding of the disease pathogenesis, of the inter-individual disease heterogeneity, and finally identify biomarkers such as gene- and protein expression signatures and individual genes and proteins that are correlated with responsiveness or non-responsiveness to single drug treatment or the combination of the two drugs. The three years duration of the combination therapy trial will further allow us to gather information on the longitudinal evolution of the identified biomarkers under treatment of MS.