Researchers at the University of Florida Health have found a way to inhibit or reverse multiple sclerosis (MS) using a novel gene therapy technique that stops the condition’s immune response in mice.
They managed to prevent a mouse version of MS by combining a brain-protein gene. The treatment produced near-complete remission in the animal models. The findings were published in the journal Molecular Therapy. Researchers claimed these findings could have significant potential for treating MS in the future.
The researchers used an adeno-associated virus (AAV), to deliver a gene responsible for a brain protein into the livers of the mice. They used an AAV because it causes a mild human response but is not known to cause disease. The virus sparked production of regulatory T-cells, which supress the immune system attack that defines MS. Researchers said the gene was targeted to the liver because it has the ability to induce immune tolerance.
'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,' said Brad E. Hoffman, Ph.D., an assistant professor in the departments of paediatrics and neuroscience at the University of Florida College of Medicine.
The protein, myelin oligodendrocyte glycoprotein, was found to be effective in preventing and reversing muscular dystrophy on its own. A group of five mouse models that received the gene therapy did not develop experimental autoimmune encephalomyelitis, which is the mouse equivalent of MS in humans. In another experiment, all but one mouse model showed a significant reversal of the disease eight days after a single gene therapy treatment.
Hoffman said he was also encouraged by the treatment’s longevity. After seven months, the mouse models that were treated with gene therapy showed no signs of disease, compared with a group of untreated mouse models that had neurological problems after 14 days.
When the protein was combined with rapamycin — a drug used to coat heart stents and prevent organ transplant rejection — its effectiveness was further improved, the researchers found. The drug was chosen because it allows helpful regulatory T-cells to proliferate while blocking undesirable effector T-cells, Hoffman said.
Among the mouse models that were given rapamycin and the gene therapy, 71% and 80% went into near-complete remission after having hind-limb paralysis. That, Hoffman said, shows the combination can be especially effective at stopping rapidly progressing paralysis.
While researchers have established how gene therapy stimulates regulatory T-cells in the liver, Hoffman said little else is known about the detailed mechanics of how that process works.