mbp-8298 and Multiple-Sclerosis

The current treatments for multiple sclerosis (MS) are, by many measures, not satisfactory. The original interferon-β therapies were not necessarily based on an extensive knowledge of the pathophysiological mechanisms of the disease. As more and more insight has been acquired about the autoimmune mechanisms of MS and, in particular, the molecular targets involved, several treatment approaches have emerged. In this chapter, we highlight both promising preclinical approaches and therapies in late stage clinical trials that have been developed as a result of the improved understanding of the molecular pathophysiology of MS. These clinical stage therapies include oral agents, monoclonal antibodies, and antigen-specific therapies. Particular emphasis is given to the molecular targets when known and any safety concerns that have arisen because, despite the need for improved efficacy, MS remains a disease in which the safety of any agent remains of paramount importance.

Topics: Alemtuzumab; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Cladribine; Crotonates; Daclizumab; Dimethyl Fumarate; Encephalomyelitis, Autoimmune, Experimental; Fingolimod Hydrochloride; Fumarates; Humans; Hydroxybutyrates; Immunoglobulin G; Immunosuppressive Agents; Immunotherapy; Mice; Multiple Sclerosis; Myelin Basic Protein; Nitriles; Peptide Fragments; Propylene Glycols; Quinolones; Rituximab; Sphingosine; Toluidines; Vaccines, DNA

To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2(+) or DR4(+)).. This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2(+) or DR4(+), or DR2(-)/DR4(-)). Upon entry of 100 DR2(-)/DR4(-) subjects, further study enrollment was limited to DR2(+) or DR4(+) subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life.. There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified.. In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo.. This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+).

Topics: Adult; Aged; Disability Evaluation; Disease Progression; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Peptide Fragments; Quality of Life; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Clinical Trials as Topic; Humans; Multiple Sclerosis; Myelin Basic Protein; Peptide Fragments

BioMS Medical Corp, under license from the University of Alberta, is developing MBP-8298, a synthetic peptide analog of myelin basic protein, for the potential treatment of multiple sclerosis. Phase II and III clinical trials of MBP-8298 are underway.

Topics: Animals; Drug Design; Humans; Multiple Sclerosis; Myelin Basic Protein; Patents as Topic; Peptide Fragments; Randomized Controlled Trials as Topic