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

Abstract

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.

Distinct gene signature revealed in white blood cells, CD4+ and CD8+ T cells in (NZBx NZW) F1 lupus mice after tolerization with anti-DNA Ig peptide

“…[1][2][3][4][5][6][7] Studies on human autoimmune diseases including SLE have reported amelioration of inflammatory responses and increases in CD4 þ CD25 þ Treg cells following treatment with self-antigen-derived peptides. [8][9][10][11][12][13][14][15][16] Similarly, self-antigen-derived peptides have also been used to induce immune tolerance and ameliorate disease in murine lupus models. 15,[17][18][19][20][21][22][23][24][25] Our group has developed a novel peptide pConsensus (pCons) that is based on MHC Class I and Class II T-cell determinants in the heavy chain region of murine anti-DNA IgG.…”

Microstructural analysis of the effects of incorporation of myelin basic protein in phospholipid layers

“…Several reports indicate that it contains epitopes for experimental autoimmune encephalomyelitis (Ohler et al 2004), a pathology which mimics multiple sclerosis. Recent clinical studies on the effects of MBP in multiple sclerosis patients have been published (Bielekova et al 2000). MBP belongs to the class of intrinsically unstructured proteins (IUP), and the unraveling of its structure is still a major unsolved problem in modern structural biology.…”

Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis

“…APLs have successfully been used as immunotherapeutic agents in experimental models of autoimmune diseases (29,30). An APL of myelin proteolipid protein, generated by substitution at a principal TCR contact residue of the encephalitogenic peptide, has been shown to prevent autoimmune encephalitis when mice were coimmunized with the APL and myelin proteolipid protein.…”

“…Although this does not ensure that a similar parallelism exists between our DR-transgenic mice and RA patients, it certainly provides a reasonable basis for development of reagents that might have therapeutic importance. Although the use of APL in the treatment of human disease is limited, 2 trials of APLs that were used to treat multiple sclerosis have produced some preliminary results (29,44). In fact, our preliminary studies, in which a low dose of rCII(N 263 , D 266 ) was administered to mice intravenously after the onset of severe arthritis, showed a reduction in the mean arthritis severity scores as compared with the controls administered PBS (Myers LK, et al: unpublished data).…”