mbp-8298 and Multiple-Sclerosis--Chronic-Progressive

One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system. 6 Weeks and 6months after treatment their PBMCs displayed a reversal of anergy with phytohemagglutinin stimulation. There was also a marked increase in their CD4(+)CD25(+hi)FoxP3(+) T-cells regulatory T-cells. These results suggest that high dose MBP8298 treatment has a profound effect on the circulating T-cells of CPMS patients, capable of reversing peripheral anergy and establishing T regulation.

Topics: CD4 Lymphocyte Count; Clonal Anergy; Compassionate Use Trials; Dose-Response Relationship, Immunologic; Follow-Up Studies; Humans; Immunotherapy; Interferon-gamma; Interleukin-17; Interleukin-2 Receptor alpha Subunit; Multiple Sclerosis, Chronic Progressive; Myelin Basic Protein; Peptide Fragments; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Treatment Outcome