Zenapax to Treat Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that preferentially affects young adults. While its etiology is unknown, current concepts assume that CD4+ helper T cells with specificity for components of the myelin sheath initiate the pathogenetic process. The activation and expansion of such autoreactive T cells involves the secretion of autocrine growth factors, particularly interleukin-2 (IL-2), and the concomitant expression of its receptor, IL-2R, on the surface of T cells. Since only activated T lymphocytes can migrate through the blood brain barrier into the CNS and induce the inflammatory process, blocking the IL-2R should have an impact on disease activity in MS. In this trial , a humanized antibody against the IL-2Ra subunit (Zenapax(Registered Trademark)) will be used to inhibit T cell activation in MS patients who have failed conventional therapy by interferon-b. We will focus on the latter group of patients, since a substantial number of patients on conventional therapy respond only partially or completely fail treatment after longer periods of time. Up to 10 patients fulfilling these criteria will be enrolled in this baseline-to-treatment, cross-over, MRI-controlled single-center phase I/II trial to assess the safety of Zenapax(Registered Trademark) treatment and, at the same time, examine the clinical course and particularly the inflammatory activity in the CNS by monthly magnetic resonance imaging (MRI). Furthermore, immunological studies will be performed in parallel to the trial in order to a) identify the impact of Zenapax(Registered Trademark) treatment on immune parameters that should be affected by the blocking of the IL-2R, and b) to improve our understanding of the relevance of activated autoreactive T lymphocytes in MS.