Nature Medicine
6, 1167 - 1175 (2000)
doi:10.1038/80516
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 ligandBibiana Bielekova1, Bonnie Goodwin1, Nancy Richert2, Irene Cortese1, Takayuki Kondo1, Ghazaleh Afshar1, Bruno Gran1, Joan Eaton1, Jack Antel3, Joseph A. Frank2, Henry F. McFarland1
& Roland Martin11
Neuroimmunology Branch, National Institute of Neurological
Disorders and Stroke, Bethesda, Maryland 20892-1400
, USA
2
Laboratory of Diagnostic Radiology Research, Clinical
Center, National Institutes of Health, Bethesda, Maryland
20892-1400, USA
3
Department of Neurology, Montreal Neurological Institute
, 3801 University Avenue, Montreal,
Quebec H3A 2B4, Canada
Correspondence should be addressed to R.M. 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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