Immunotherapy Reverses Multiple Sclerosis in Mice

Gene therapy is a technique that involves the use of genes – replacing them, inactivating them, or introducing new ones - to treat or prevent a specific disease. As of this year, a study was conducted to indicate how the progression of MS in mice can be prevented or reversed.

The study, “Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-Inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis” was published in the journal Molecular Therapy. It revealed that the liver has the potential to stop harmful immune responses that trigger MS. Using gene therapy, Brad E. Hoffman, a research immunologist and associate professor in the departments of pediatrics and neuroscience at the University of Florida College of Medicine, and his research team were able to reverse severe paralysis in mice model versions of the disease. “We were very impressed with the results. We expected there to be a reversal or at least a dampening of the disease. We were quite surprised we had that level and magnitude of response, and how long the reversal lasted” said Hoffman. They hope that the study will open up doors to new treatment developments for treating MS in humans.

How was this study performed?

The researchers used a harmless virus, known as adeno-associated virus (AAV), to transfer myelin oligodendrocyte glycoprotein (MOG) - a myelin sheath protein believed to be an important part of brain myelin – into the liver cells of mice. Myelin is known as the protective coating that surrounds the nerve cells and whose function is of great significance in preventing MS. “Traditional AAV gene therapy has been focused on delivering a transgene that produces a therapeutic protein. Here we use the platform purposely to induce specific regulatory cells in order to restore immune tolerance and reverse an autoimmune disease” said Hoffman.

The team’s report showed that MOG in the liver sparked the production of MOG-specific regulatory T-cells, also known as Tregs. Tregs have the potential to prevent immune attacks on the protein. “Using a clinically tested gene therapy platform, we are able to induce very specific regulatory cells that target the self-reactive cells that are responsible for causing multiple sclerosis. In contrast, most current therapies for autoimmune diseases such as multiple sclerosis are based on general immune suppression, which has various side effects or complications” said Hoffman. In other words, the team exposed the mice to experimental autoimmune encephalomyelitis (EAE), which is an animal version of MS. The gene therapy inducted protein, MOG, was found to be effective in preventing and reversing MS on its own. The researchers noted in their paper that this is not the first time this approach has been tested on animals. “Leveraging the tolerogenic nature of the liver, hepatic gene transfer has successfully been used to induce robust transgene tolerance in large- and small-animal disease models” wrote the team in their published report.

The study was conducted over the course of 7 months and at the beginning, the mice that were treated with gene therapy showed no signs of remission and had higher levels of Tregs in their blood, as opposed to the control group. Even when the researchers tried to trigger MS in the mice, they still remained in remission, supporting the notion that the mechanism of Tregs works to promote immune tolerance. “We waited several more months, and we rechallenged the mice a second time, and it still prevented in almost 100 percent of them” said Hoffman.

Read on to learn more about the implications of this research.