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

Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) repres ents one candidate antigen; therefore, it was chosen to design an altered p eptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this a ltered peptide ligand documented that it was poorly tolerated at the dose t ested, and the trial had therefore to be halted. Improvement or worsening o f clinical or magnetic resonance imaging parameters could not be demonstrat ed in this small group of individuals because of the short treatment durati on. Three patients developed exacerbations of multiple sclerosis, and in tw o this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic p rotein peptide (a.a. 83-99) in a subgroup of patients. These data raise imp ortant considerations for the use of specific immunotherapies in general.