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Reprogramming the immune system in people with MS

Background: What is targeted in MS?

MS is classified as an autoimmune disease, which means the body's own immune system recognizes components that are naturally found in the body and attacks them as if they are foreign pathogens. In general, each autoimmune disease involves a different target in the body; with the case of MS, that target is myelin. Myelin is a substance which surrounds nerve fibers in the brain and spinal cord, allowing them to send chemical signals which enable the body to perform basic functions including walking, sleeping, speaking and learning. In people who have MS, damage to myelin leads to many neurologic symptoms ranging from mild numbness to paralysis.

For decades, MS researchers have struggled to find ways to reprogram the immune cells that attack myelin – to prevent them from seeing myelin as a target. Early this June, an international research team led by Dr. Roland Martin from the Institute for Neuroimmunology and Clinical MS Research, Hamburg and University Hospital Zürick published results from a clinical trial involving a particular method of reprogramming myelin-reacting immune cells. Results showed that the treatment is safe for MS patients and induces beneficial changes that lasted over time. 

The Study: Antigen-specific tolerance

Nine people with relapsing-remitting or secondary-progressive MS participated in a phase 1 clinical trial. In the trial, each person’s own white blood cells were used to deliver myelin antigens – specific components of myelin that are believed to be attacked in MS – throughout the body.  This blood cell transfusion procedure is designed to produce an effect called antigen-specific tolerance. Essentially, this effect renders harmful immune cells ‘tolerant’ to the myelin antigens they are exposed to. Following treatment, the immune cells no longer recognize myelin as a target and their damaging effects are reduced.

This study was developed from decades of pre-clinical lab work conducted by Dr. Stephen Miller from Northwestern University Feinberg School of Medicine. Dr. Miller’s work involved inducing myelin tolerance in mice with MS-like disease. He and colleagues observed a significant reduction in the onset and severity of relapses in the MS mice that were treated with this procedure.  The next step was to design a clinical trial in humans to evaluate the feasibility, safety and tolerability (or the body’s reaction) of the antigen-specific tolerance method.

Results:

Results of the phase I clinical trial revealed that 6 out of the 9 patients who underwent blood cell transfusion experienced no relapses during the first 3 months after treatment. Two people who showed increased MS disease activity just prior to the study experienced one MS relapse 10 to 16 days after receiving the treatment. Overall, the treatment caused no adverse effects. More importantly, testing showed their immune systems' reactivity to myelin was dramatically reduced. Post treatment testing also showed there was no reduction in the normal function of the immune system that protects individuals against outside invaders. Other effective MS therapies reduce or suppress the entire system.

Relevance:

The phase 1 clinical trial provides insights into a treatment based on tolerization – a process by which immune cells implicated in MS become tolerant to components of myelin and no longer exhibit harmful effects against it. This work marks an important advancement in MS research, as it is an example of applying preclinical findings in animals to humans (or the term bench to bedside).  These early results have demonstrated that this unique treatment is safe, tolerable, and able to diminish autoimmune activity in people with MS. The results pave the way for development of further clinical trials that will test the safety and efficacy of this potential MS treatment in a larger cohort of patients.

The trial results have stirred interest across the whole spectrum of autoimmune diseases. If this approach proves out over the next several years of clinical trials, a similar strategy could be used to control auto-immune diseases ranging from diabetes to peanut allergies as well as multiple sclerosis.

Source:
Lutterotti A et al. Antigen-Specific Tolerance by Autologous Myelin Peptide-Coupled Cells: A Phase 1 Trial in Multiple Sclerosis. Sci Transl Med 2013 Jun 5; 5(188):188ra75 doi:10.1126/scitranslmed.3006168