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.
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.
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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1. Lutterotti A, Yousef S, Sputtek A, et al. Antigen-Specific Tolerance by Autologous Myelin Peptide-Coupled Cells: A Phase 1 Trial in Multiple Sclerosis. Science Translational Medicine June 2013; 5(188):188ra75. DOI: 10.1126/scitranslmed.3006168. Accessed at http://stm.sciencemag.org/content/5/188/188ra75
2. Big multiple sclerosis breakthrough: Phase 1 trial safely resets patients' immune systems and reduces attack on myelin protein. Northwestern Press Release. Published June 5, 2013. Accessed at http://www.eurekalert.org/pub_releases/2013-06/nu-bms053113.php
3. “Breakthrough Nanoparticle Halts Multiple Sclerosis: New nanotechnology can be used for Type 1 diabetes, food allergies and asthma” by Marla Paul, Northwestern News. Published November 19, 2012. Accessed at http://www.northwestern.edu/newscenter/stories/2012/11/breakthrough-nanoparticle-halts-multiple-sclerosis.html
4. “Multiple Sclerosis Breakthrough Resets Patients’ Immune Systems” by Jeri Burtchell, HealthlineNews. Published June 5, 2013. Accessed at http://www.healthline.com/health-news/ms-breakthrough-treatment-resets-immune-system-stops-myelin-attacks-060513