Researchers use Gene Therapy to Build Immune Tolerance

Stuart SchlossmanMS Genetic Research

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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