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Saturday, May 31, 2014

Tolerance-Directed Immunotherapies: The Future of MS Treatment?

Stephen D. Miller, PhD
Stephen D. Miller, PhD

Precisely targeted therapies that establish immune cell tolerance of specific antigens may enable clinicians to move in coming years from managing the symptoms of MS and other autoimmune diseases via immunosuppression to shutting down the underlying disease processes on a long-term or even permanent basis.

That was the message Stephen D. Miller, PhD, delivered to health-care professionals in his keynote lecture that opened the 2014 Cooperative Meeting of CMSC and ACTRIMS in Dallas, TX yesterday. Dr. Miller, the Judy Guggenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine, added that the ability to deliver tolerance-directed immunotherapies via biodegradable polymer-based nanoparticles – rather than through complex and costly procedures that extract, treat, and then re-infuse a patient’s white blood cells – offers the prospect of the therapies being widely accessible.

“The implications for immune-mediated diseases such as multiple sclerosis (MS), Type 1 diabetes, arthritis, asthma, and food allergies are profound,” Dr. Miller said in an interview previewing his lecture. “Our current approach to autoimmune disease treatment generally involves suppression of the immune system, with all the attendant risks of making a person more susceptible to infections, cancer, and other conditions. Tolerance-directed therapies affect only the pathogenic autoreactive T cells that react to a specific antigen, and work to ‘re-set’ those cells to avoid a response rather than to suppress a response. The precision of this targeting means that we would not have the broad impact on the overall immune system that current immunosupression approaches do. Further, if we can establish tolerance to the antigen, we can stop the autoimmune disease process rather than having to content ourselves with dealing with its symptoms.”

Intriguing research
Dr. Miller, who has researched autoimmune diseases for more than 30 years, hopes to launch a Phase 1 trial of a tolerance-directed immunotherapy delivered via poly (D,L-lactide-co-glycolide) (PLG) nanoparticles within the next year to year and a half. Last year, he and colleagues at Northwestern and in Hamburg, Germany published the results of a 9-patient study which found that a tolerance-directed immunotherapy for MS was safe and reduced the patients’ immune systems’ reactivity to myelin by 50 to 75 percent. However, that study employed a sophisticated method for extracting patients’ white blood cells (WBCs), processing them to deliver myelin antigens into the patients’ bodies in a way that would help develop tolerance for the antigens, and then re-infusing the WBCs. Dr. Miller’s planned Phase 1 study, for which he is securing funding, would avoid the complicated extraction/re-infusion process by delivering antigens via biodegradable nanoparticle. In a murine study reported in 2012, Dr. Miller and colleagues found that polymer nanoparticles were an effective vehicle for delivering antigens in a way that prompted the immune system to stop attacking myelin. That approach halted a model of relapsing-remitting MS in mice.

An opportunity to stop the disease process

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