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GEN News Highlights : Jun 5, 2013
Stopping MS Inflammation in Its Tracks
Scientists from Northwestern University’s Feinberg School of Medicine, University Hospital Zurich, and University Medical Center Hamburg-Eppendorf in Germany reported in a paper published in the June 5 issue of Science Translational Medicine that a Phase I clinical trial testing a treatment to “reset” the immune systems of multiple sclerosis patients reduced their antimyelin immune responses by 50 to 75%.
Multiple sclerosis (MS), a disease of the brain and spinal cord, is thought to result from an autoimmune attack directed against antigens in the central nervous system. In MS, the immune system attacks myelin, the insulating layer that forms around nerves in the spinal cord, brain and optic nerve. When the insulation is destroyed, nerve signals can't be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness.
In this study, the authors sought to induce immune tolerance to myelin antigens among MS patients, thereby preventing or mitigating the immune system antimyelin attack. The aim of this trial was to assess the feasibility, safety, and tolerability of a tolerization regimen using a single infusion of autologous (individual patient-specific) peripheral blood mononuclear cells (PBMS) chemically coupled with seven myelin peptides. The open-label, single center, dose-escalation study was performed in seven relapsing-remitting and two secondary progressive MS patients, all of whom had to show T-cell reactivity against at least one of the myelin peptides used in the trial, and who were off treatment for standard therapies.
Study results showed that administration of antigen-coupled PBMS cells was feasible, had a favorable safety profile, and was well tolerated by patients. Patients receiving the higher doses (>1 × 109) of peptide-coupled cells had a decrease in antigen-specific T-cell responses following the tolerization regimen.
"The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells," said Stephen Miller, Ph.D., the Judy Gugenheim research professor of microbiology-immunology at Northwestern University Feinberg School of Medicine. "Our approach leaves the function of the normal immune system intact. That's the holy grail." Most current MS treatments are immunosuppressive, making patients susceptible to a variety of infections.
Most of the patients who received high doses of the antigen-coupled blood cells did not show any new brain lesions or symptomatic relapses up to the end of the study’s six month follow-up period. The results, the authors said, also suggest that this tolerization approach is safe and may prove useful for preventing inflammation in MS patients. Further, by attaching different antigens to the PBMCs, the technique could help treat other autoimmune and allergic diseases.
The MS human trial relates directly to a study recently published by Dr. Miller, in which he used nanoparticles—rather than blood cells—to deliver the myelin antigen. Miller's study showed the nanoparticles, which are potentially less expensive and more accessible to a general population, could be as effective as the white blood cells as delivery vehicles. This nanoparticle technology has been licensed to Cour Pharmaceutical Development Company and is in preclinical development.
The study, “Antigen-Specific Tolerance by Autologous Myelin Peptide–Coupled Cells,” was published in the June 5 issue of Science Translational Medicine.
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