Resetting the Immune System: Phase 1 Trial Shows Safety of New MS Therapeutic Approach

Multiple sclerosis is an autoimmune disease in which the immune system goes rogue and attacks and destroys myelin, the fatty, protective layer of tissue which insulates nerves and helps to transmit electrical signals throughout the body.  It is thought that the immune system begins to perceive the myelin to be an invader (antigen) and tries to remove it, causing damage to the central nervous system in MS patients.

When the myelin has been damaged or stripped, a process called demyelination, the exposed neurons do not function well.  Symptoms range from mild to severe and may include numbness and tingling, weakness or paralysis, loss of vision, lack of coordination or balance, loss of bladder control, cognitive difficulties, or even depression and anxiety.

Current MS therapies aim to stop or slow down the body’s attack on itself, protecting myelin, in a variety of immuno-modulating ways.  Of the nine FDA-approved therapies for relapsing-remitting MS, only Tysabri and Gilenya are considered immunosuppressants.  Other immunosuppressants sometimes used to combat progressive MS include Novantrone, Cytoxan, Imuran, and methotrexate.  Solumedrol is a powerful corticosteroid and immunosuppressant used to quickly calm down inflammation in the body during an MS relapse.

Stopping the Attack on Myelin

Results from a Phase I clinical trial of a new treatment designed to reset the immune system and stop the attack on myelin in MS patients show that the therapy was safe and highly effective.  This small first-in-human trial (n=9) conducted in Germany is the translation of more than 30 years of preclinical research conducted at Northwestern University by Dr. Stephen Miller, an investigator associated with the Myelin Repair Foundation.  The study, a collaboration between Northwestern University’s Feinberg School of Medicine, University Hospital Zurich in Switzerland, and University Medical Center Hamburg-Eppendorf in Germany, was published in the journal Science Translational Medicine.

The study involved taking blood samples from each of the nine participants, separating out white blood cells, and attaching bits of seven different myelin peptides to these cells.  Then by intravenously injecting each patient with their own modified T-cells, researchers were able to deliver up to 3 billion myelin antigens into the bloodstream in a way that encouraged the immune system to recognize them as harmless and develop a tolerance for the antigens.

Before the trial, all patients had to show T-cell reactivity against at least one of the myelin peptides used in the trial.  After the procedure, patients' immune systems' reactivity to myelin was reduced by 50 to 75 percent.  One month after the procedure, researchers tested patients’ immune response to tetanus, which remained strong, demonstrating that the treatment’s immune effect was specific only to myelin.

"The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells," said Dr. Miller. "Our approach leaves the function of the normal immune system intact. That's the holy grail."

The study satisfied its primary goal in demonstrating the treatment’s safety and tolerability, while causing no adverse effect in MS patients.  Safety and tolerability is the main focus of Phase I trials.  Researchers noted that patients who received the highest dose of white blood cells showed the greatest reduction in myelin reactivity.

What’s next?

Scientists are currently trying to raise $1.5 million to launch a Phase 2 trial to see if the new treatment can prevent the progression of MS in humans.  Dr. Miller’s preclinical research, using nanoparticles to deliver myelin-specific antigens, demonstrated that the treatment stopped the progression of relapsing-remitting MS in mice.   But the approach needs to be tested in a larger group of patients to validate safety and efficacy.

"In the phase 2 trial we want to treat patients as early as possible in the disease before they have paralysis due to myelin damage." Miller said. "Once the myelin is destroyed, it's hard to repair that."

“The use of nanoparticles would avoid the intrusive, complex, rather lengthy and costly process of collecting, purifying, and modifying the patient's white blood cells,” said Miller. “The particles are biodegradable and can be manufactured easily to FDA standards and would provide an 'off-the-shelf' material to which various antigens could be easily and efficiently attached.”

Using nanoparticles is potentially cheaper as they can be produced in a laboratory and standardized for manufacturing.  The nanoparticles used in Miller’s lab are made of a polymer, consisting of lactic acid and glycolic acid, called poly(lactide-co-glycolide) or PLG, which is most commonly used for biodegradable sutures.

This therapeutic approach - using a patient’s white blood cells or nanoparticles to introduce specific antigens to a patient’s immune system to induce a tolerance to the antigen - may be useful in treating other autoimmune or allergic diseases in which the targeted antigens are known.  Previously published preclinical research by Miller showed the therapy's effectiveness for type 1 diabetes and airway allergy (asthma) and peanut allergy.

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This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

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