The ultimate goal of immunotherapy in multiple sclerosis (MS) is to find immunologically specific, relatively non-toxic forms of therapy. Currently available immunomodulatory therapies have demonstrated the ability to modify disease outcomes in patients with relapsing remitting disease. Our understanding of the immunopathogenesis of MS implicates T cell activation as an important step in the pathogenesis of this disease. The CD40-CD40L pathway of T cell co-stimulation plays a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) the animal model of MS. Furthermore, CD40 was found in MS brain and evidence for the involvement of this co-stimulatory pathway in MS pathogenesis is accumulating. Treatment of animals with anti-CD40L suppresses EAE. initial safety studies in humans with anti-CD40L showed that this treatment could safely be administered to patients. Thus, our primary objective in this study is to evaluate in a pilot study two doses of anti-CD40L therapy versus placebo in patients with MS. Safety will be initially investigated in 5 individual patients who are treated with a single dose of anti-CD40L and evaluated by clinical and MRI criteria as well as safety blood tests. Dose requirements will be investigated in a randomized double-blind placebo controlled 2 dose study. The outcome measures will be progression on clinical disease scales, number of relapses, and time to sustained progression. Secondary outcome measures will include T2 lesion volume on MRI and number of GD enhancing lesions.
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