💊 Towards new treatments for autoimmune diseases

A study published in the journal PNAS demonstrates that it might be possible to slow the progression of certain autoimmune diseases using drugs that would interfere with the antibodies responsible for these conditions. In mice with an autoimmune neurological disease, a drug of this type led to a decrease in the severity of symptoms and a restoration of certain functions, including mobility.

"This proof of concept opens the way to a new range of treatments for autoimmune diseases," says the lead researcher of the study, Luc Vallières, a professor at the Faculty of Medicine of Laval University and researcher at the research center of the CHU de Québec - Université Laval.


For reasons that are not yet fully understood, 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," specifies Professor Vallières.

Each autoantibody has a specific anatomical target to which it binds. Once this binding is established, the autoantibody mobilizes cells of the immune system that attack this target, causing inflammation and destruction of the tissue in question.

The approach developed by Luc Vallières's team involves producing synthetic antibodies that recognize the same targets as the autoantibodies and take them over. A mutation introduced into these antibodies through genetic manipulation prevents them from triggering the immune response that leads to an autoimmune disease.

The scientists 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 the myelin, the protective sheath surrounding the elongated part of nerve cells. The resulting inflammation and destruction of the myelin notably lead to the appearance of locomotor disorders.


However, the inflammatory process takes a different trajectory when the scientists administer inactive synthetic antibodies targeting the MOG protein to the mice. "The symptoms of the disease are then attenuated. Furthermore, a greater proportion of mice recover their functional abilities," emphasizes Professor Vallières.

According to the researcher, this concept could be extrapolated to other human autoimmune diseases that involve autoantibodies. "In each case, we would need to find the responsible autoantibody or antibodies and produce modified antibodies that can bind to the same targets. Our next goals are to produce modified human antibodies and, eventually, to test them in the context of clinical trials."

The article published in PNAS is authored by 15 scientists, including 8 members of the research center of the 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. The other signatories are Qun Zhou, Julie Jaworski and Anna Park, from the pharmaceutical company Sanofi 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 University of Montreal, and Steven Kerfoot, from the University of Western Ontario.