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Wednesday, May 7, 2014

Researchers use Gene Therapy to Build Immune Tolerance

Researchers use Gene Therapy to Build Immune Tolerance

University of Florida researchers have received a $40,000 grant from the National Multiple Sclerosis Society to test a gene therapy technique in mice that aims to help the body not treat itself like a foreign invader — a process referred to as immune tolerance — in the earliest stages of multiple sclerosis.

“In previous years, we have learned a lot about how to manipulate tolerance using gene therapy,” said Brad E. Hoffman, Ph.D., an assistant professor of pediatrics in the UF College of Medicine. “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.”

Typically, gene therapy is used to correct a faulty gene in the body. In this case, researchers will deliver a gene responsible for a brain protein into the liver, via the harmless virus AAV, in hopes that it will spark production of regulatory T cells. These T cells, which suppress the immune system, are crucial because they could effectively shut down the immune attack in the brain, Hoffman said. The researchers are injecting the gene specifically into the liver because the organ filters out unwanted immune responses.

“Everything filters through the liver for detoxification,” Hoffman said. “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 research teams across the country are trying to spark immune tolerance to combat MS, too. However those studies involve developing treatments personalized for specific patients. The UF researchers’ work is novel because they hope to develop a technique that could be used on a wide number of patients.

“Everyone has different types of T regulatory cells and receptors,” Hoffman said. “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.”

Although gene therapy has yet to be used to correct autoimmune disorders such as MS, the foundations for the study are rooted in research that Hoffman’s team has performed while studying gene therapy for hemophilia. During these studies, the team was able to induce immune tolerance in mice, and Hoffman hopes the techniques will one day be able to help people with multiple sclerosis, too.

“Will we be able to cure MS? That would be ideal, but our strategy is more likely to result in suppressing the immune response to the nervous system,” he said. “If you suppress the immune response, you will suppress the neurodegenerative effects and hopefully maintain a higher quality of life.”




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