Published in the Journal of Molecular Therapy, researchers at the University of Florida have discovered that by combining an existing medication and a brain-protein gene, they were able to prevent and/or nearly reverse versions of multiple sclerosis in mice.
Approximately 2.3 million people suffer from Multiple sclerosis worldwide; it is the most common neurological disease in young adults. An auto-immune disorder, it begins with the immune system attacking the myelin sheath (similar to wire insulation) around nerve fibers. The nerves then begin to misfire, creating multiple symptoms such as vision problems, muscle weakness, lack of muscle coordination, and speech problems. At this time it is an incurable disease that can usually be managed to varying degrees with different medications.
Using a harmless adeno-associated virus, scientists implanted a brain gene protein into mouse livers. This process then produced regulatory T cells which suppress the multiple sclerosis immune system attack.
Brad E. Hoffman, Ph.D, assistant professor in the departments of pediatrics and neuroscience at the University of Florida College of Medicine states: “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.” He goes on to explain that a myelin oligodendrocyte glycoprotein, was found to be effective in preventing and reversing muscular dystrophy on its own. A group of five mice who received the gene therapy did not develop autoimmune encephalomyelitis – the mouse equivalent of multiple sclerosis in humans. In another experiment, after a single gene therapy treatment, a significant reversal of the disease was demonstrated in all but one mouse within an eight-day period.
In another seven months, Hoffman was again encouraged by the longevity of the treatment. Compared to untreated mice with neurological problems after 14 days, the mice with gene therapy showed no signs of disease,
An even greater improvement was noted by Hoffman and his team when they combined rapamycin (a drug used to coat heart stents and prevent organ transplant rejection). Researchers felt that this drug would allow regulatory T-Cells to increase while at the same time block undesirable effector T-cells. Of the mice that were treated with this formula, 71-80% went into remission after having suffered paralysis of the rear legs. Hoffman feels this could be very effective at stopping rapidly progressing paralysis in humans.
Even though researchers established that gene therapy can stimulate regulatory liver T cells, it is unknown exactly how that process works. Researchers need to target the other proteins implicated in multiple sclerosis. Before human clinical trials can begin, further research involving other models will be needed, Hoffman said. However, he is extremely optimistic that this gene therapy will be effective in humans. “If we can provide long-term remission for people and a long-term quality of life, that is a very promising outcome.”
