Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83–99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83–99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general.
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We thank T. Staehelin (Novartis, Basel, Switzerland) and P. Conlon (Neurocrine Biosciences, San Diego, California, California) for comments, W.E. Biddison, C.S. Stuerzebecher (Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health) and M. Connors (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for critical reading of the manuscript, L. Tranquill and S. Yun (Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health) for technical assistance, H. Griffith and J. McCartin R.N. for nursing assistance, and J. Black and R. Hill for assistance in MRI collection. The phase II clinical trial of CGP 77116 is supported by Neurocrine, Biosciences (San Diego, California) and Novartis (Basel, Switzerland).
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Bielekova, B., Goodwin, B., Richert, N. et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand. Nat Med 6, 1167–1175 (2000). https://doi.org/10.1038/80516
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