Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial

Abstract

In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

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.…”

Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis

“…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).…”

Antigen-Specific Therapy of Multiple Sclerosis: The Long-Sought Magic Bullet

“…These responses had characteristics of a T helper 2 type associated with production of IL-5. 9,28 In some patients such T helper 2 responses to both myelin basic protein and to its altered peptide ligand were monitored four years after cessation of therapy with the APL. 29 In an open label trial in eight patients with MS at the National Institutes of Health there was overall no clinical worsening in clinical or MRI parameters.…”

“…Here I shall review what so far has been attempted in man, and the challenges that we face in devising such a therapy that would be truly worthy of the title that I think Paul Ehrlich intended, when he first unveiled the term "magic bullet". 7 In this article I shall explore four ongoing examples where investigators are attempting antigen specific approaches for the treatment of MS: two trials with the same altered peptide ligand directed to the 83-99 peptide of myelin basic protein 8,9 ; a trial of therapy with a peptide to myelin basic protein 82-98 10 ; and a trial of a DNA vaccine directed to the entire myelin basic protein molecule. 11 Earlier attempts by Jonas Salk and colleagues to tolerize the immune system with porcine myelin basic protein, 12,13 and by Weiner and colleagues 14 to tolerize via orally delivering myelin antigens will be discussed in context.…”