Mechanistic Studies of Teriflunomide in RRMS
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Observational

Summary: 
      This study is to address the mechanism of action of teriflunomide in a phase IV open label
      trial with Teriflunomide in multiple sclerosis. Researchers will recruit 20 relapsing
      remitting multiple sclerosis patients (Group 1) start on treatment with teriflunomide
      (Aubagio). Patients will be enrolled from the Multiple Sclerosis Center at the University of
      Michigan Health System in Ann Arbor. Meanwhile, 10 healthy controls will be recruited, to
      establish a healthy baseline for B and T cells, which are affected by both MS and its
      treatment (Group 2). This Study will collect baseline pre-treatment blood samples
      periodically for up to 2 years. Blood biomarker changes will be correlated with clinical
      response to teriflunomide treatment intervention.
    

Detailed description: 
      Multiple sclerosis is the most common autoimmune inflammatory and debilitating chronic
      demyelinating disease of the central nervous system mainly affecting young adults. There is a
      tremendous need to understand the mechanism of action of the treatment and how they might
      work in multiple sclerosis patients. Most recently, teriflunomide (AubagioTM) has been
      demonstrated to act as an immune modulatory therapy for patients with multiple sclerosis.
      Although one biochemical mechanism of action is understood to be related to inhibition of
      dihydroorotate dehydrogenase (DHODH) which affects synthesis of pyrimidine nucleotides, there
      have also been reports that the functions of regulatory T cells are promoted by these drugs
      independent of DHODH. Much accumulating evidence suggests that specialized subsets of B
      lymphocytes are important inducers of regulatory T cells, as well as having killer functions
      that may preferentially target TH1 and TH17 cells.

      This study aims to address the mechanism of action of teriflunomide in a phase IV open label
      trial with Teriflunomide in multiple sclerosis
    

Intervention name(s): Teriflunomide
Intervention type(s): Drug
Intervention description(s): AUBAGIO® (teriflunomide) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), which inhibits pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase.
Other intervention name(s): Aubagio
Intervention MeSH terms: Teriflunomide
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        A total of 20 multiple sclerosis (MS) patients and 10 healthy controls will be recruited to
        voluntarily donate blood for the study. Blood samples will be collected prior to starting
        teriflunomide treatment (baseline) and after 3, 6, 9, 12, 18 and 24 months of treatment
        (+/- 2 weeks).
      
Biospecimen description: 
      Blood will be collected after 3, 6, 9, 12, 18 and 24 months of treatment.
    
Keywords: Teriflunomide; B cell; T cell; cytokines