Biomarkers in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      This study will identify biomarkers (genes and proteins) in patients with relapsing-remitting
      multiple sclerosis (MS) and link them with clinical disease parameters, such as the extent of
      inflammation and rate of disease progression, to try to better understand the disease. It
      will examine how the biomarkers may be related to disease development and progression and
      differences among patients' symptoms and response to treatment.

      Patients with relapsing-remitting MS between 18 and 60 years of age who are enrolled in the
      multi-institutional MS-CombiRx trial may be eligible for this sub-study. Participants have
      blood tests when they enter the MS-CombiRx study and again after 6 months, 1 year, and 3
      years for analysis for genetic and protein analysis.
    

Detailed description: 
      OBJECTIVE: 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.
    

Keywords: Neuroimmunology; Demyelinating Disease; Genetics; Proteins