Research team develops new drug to block antibodies involved in multiple sclerosis-like disease
A study published today in the journal PNAS shows that it may be possible to slow the progression of certain autoimmune diseases using drugs that interfere with the antibodies responsible for these pathologies. In mice suffering from an autoimmune neurological disease, a drug of this type reduced the severity of symptoms and restored certain functions, including mobility.
"This proof-of-concept opens the way to a new range of treatments for autoimmune diseases", says study leader Luc Vallières, Professor in the Faculty of Medicine at Université Laval and researcher at the Centre de recherche du CHU de Québec - Université Laval
For reasons we still don’t fully understand, the antibodies we produce to defend ourselves against microorganisms or other foreign bodies can sometimes turn against us. "These autoantibodies are present in most autoimmune diseases," explains Professor Vallières.
Each autoantibody has a specific anatomical target to which it binds. Once this binding is established, the autoantibody mobilizes immune system cells to attack this target, causing inflammation and destruction of the tissue in question.
The approach developed by Luc Vallières’ team involves producing synthetic antibodies that recognize and hijack the same targets as autoantibodies. A mutation introduced into these antibodies by genetic manipulation prevents them from triggering the immune response leading to autoimmune disease.
Scientists have demonstrated the validity of this approach using mice that develop an autoimmune disease called MOGAD. Recently identified in humans, this disease is similar to multiple sclerosis. It involves autoantibodies that target the MOG protein present in myelin, the protective sheath that surrounds the elongated part of nerve cells. The ensuing inflammation and destruction of myelin can lead to locomotor disorders.
However, the inflammatory process takes a different trajectory when the scientists administer inactivated synthetic antibodies targeting the MOG protein to the mice. "The symptoms of the disease are then attenuated. What’s more, a greater proportion of the mice regain their functional capacity," points out Professor Vallières.
According to the researcher, this concept could be extrapolated to other human autoimmune diseases involving autoantibodies. "In each case, we need to find the autoantibody(s) responsible and produce modified antibodies that can bind to the same targets. Our next goals are to produce modified human antibodies and, eventually, test them in clinical trials."
The PNAS article is signed by 15 scientists, including 8 members of the Centre de recherche du CHU de Québec - Université Laval. They are Reza Taghipour-Mirakmahaleh, Françoise Morin, Yu Zhang, Louis Bourhoven, Louis-Charles Béland, Juan Manuel Dominguez, Jacques Corbeil and Luc Vallières. Other signatories are Qun Zhou, Julie Jaworski and Anna Park, from the Sanofi pharmaceutical company in Boston, Eoin Flanagan, from the Mayo Clinic in Rochester, USA, Romain Marignier, from the Pierre Wertheimer Neurological Hospital in France, Catherine Larochelle, from the Université de Montréal, and Steven Kerfoot, from the University of Western Ontario.
