Multiple sclerosis (MS) is a disease whereby the immune system attacks myelin (fat wrappings) around axons, leaving them exposed. Destruction of myelin generates poor electrical conduction of ions and a lack of communication in the nervous system. Imagine if researchers could find a way to stop the immune response before the disease becomes debilitating. Researchers at the University of Florida have received a $40,000 grant from the National Multiple Sclerosis Society to test a gene therapy protocol in mice. This therapy has been developed to help the body not treat itself as a foreign entity, a process referred to as immune tolerance. This therapy is meant to treat the earliest stages of MS. If immune tolerance can be re-established, the immune attack could be stopped. This may prove useful for a wide number patients.
According to Brad E. Hoffman, Ph.D., assistant professor of pediatrics at the University of Florida College of Medicine, “In previous years, we have learned a lot about how to manipulate tolerance using gene therapy. Tolerance is your body’s way of not responding to substances that would otherwise induce an immune response so you don’t have an immune response to everything. In multiple sclerosis, the body loses that ability to distinguish between self and not-self so it starts to attack its own nervous system cells.”
The National Multiple Sclerosis Society reports approximately 2.3 million people have MS globally. These patients suffer from vision loss, fatigue, speech slurring, odd sensations and lack of mobility. Late stage MS can lead to blindness and paralysis.
Gene therapy is often used to correct a bad gene. In gene therapy, researchers will deliver a gene that codes for a brain protein into the liver by way of the Adeno-associated virus (AAV). Researchers believe that this gene will be able to induce production of regulatory T cells which will suppress the immune function.
According to Hoffman, “Everything filters through the liver for detoxification. Because of this, the liver has an innate capacity to induce immune tolerance. We have learned in other gene therapy studies that it is possible for the liver to make cells tolerant to the gene you are putting in.” Other laboratories are trying to initiate immune tolerance by developing personalized therapies for specific patients. However, the UF studies are novel in that they hope to develop therapies that could be used on a wide number of patients. Hoffman notes, “Everyone has different types of T regulatory cells and receptors. By injecting a gene responsible for a brain protein, we are allowing an individual’s body to make the specific T regulatory cells it needs. If it works, this is potentially more clinically feasible, cost-effective and translatable for a large scale.”
To date, gene therapy has not been administered to alter autoimmune diseases such as multiple sclerosis. Nevertheless, the groundwork for the study is rooted in earlier research by Hoffman and colleagues while studying gene therapy for hemophilia. During these earlier studies, Hoffman and his team have been able to induce immune tolerance in mice.
Hoffman remarks, Will we be able to cure MS? He admits this would be ideal, however their strategy is more likely to suppress the immune response to the nervous system. This should suppress the neurodegenerative effects and provide for a higher quality of life.