Antigen-specific therapies for the treatment of multiple sclerosis: a clinical trial update.
Within the past year a host of antigen-specific therapies for multiple sclerosis (MS) progressed along the path from IND submission to FDA approval. The Immune Response Corporation vaccinated patients with a Vbeta6 peptide, demonstrating that the vaccine was immunogenic, well tolerated, and reduced the number of Vbeta6+ T-cells in the cerebrospinal fluid (CSF). Connetics Corp. conducted a Phase I/II trial on chronic progressive MS patients vaccinated with CDR2 peptides from TCR Vbeta55.2 and found that patients with a measurable response to the vaccine remained clinically stable for a year. A study at the University of Alberta MS Patient Care and Research Clinic demonstrated that intrathecal injection of a B cell/T cell epitope of myelin basic protein (MBP) decreased the level of antiMBP antibody, but iv. administration did not decrease the relapse rate. AutoImmune Inc. completed a Phase III trial of oral myelin in the spring of 1997 which failed to show a statistical difference between those patients fed placebo and those fed daily capsules of myelin protein (Myoral). Three phase I trials of iv. myelin antigen(s) were initiated: MP4 (Alexion Pharmaceuticals, Inc.), a recombinant fusion of myelin basic protein and proteolipid protein; AG284 (Anergen, Inc.), a solubilised HLA-DR2:MBP peptide complex; and NBI-5788 (Neurocrine Biosciences, Inc.), an altered peptide ligand of an immunodominant MBP T-cell epitope. Following the conclusion of a successful Phase III clinical trial, TEVA Pharmaceutical Industries LTD received FDA approval to market Copaxone (glatiramer acetate) for the treatment of relapsing-remitting MS in December of 1996 and launched the product in 1997. The recent preclinical research and clinical trial status of these antigen-specific MS therapeutics are summarized in this review.
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Department of Immunology, Anergen, Inc., 301 Penobscot Drive, Redwood City, CA 94063, USA.