Novel Gene Therapy Reverses Paralysis in Mice with Multiple Sclerosis

Mice treated prophylactically were protected from developing multiple sclerosis and neurological deficits.

Scientists employed a novel gene therapy technique to reverse and prevent the development of multiple sclerosis (MS) in mice.

For the study, published in Molecular Therapy, investigators used the adeno-associated virus to deliver a gene responsible for a brain protein to the livers of the mouse models. The gene was targeted to the liver because it can induce immune tolerance, and the adeno-associated virus jumpstarted the production of regulatory T cells.

“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 investigator Brad E. Hoffman, PhD.

The findings showed the protein myelin oligodendrocyte glycoprotein was effective in preventing and reversing muscular dystrophy on its own, the authors noted.

In one experiment, a group of 5 mouse models administered the gene therapy did not develop experimental autoimmune encephalomyelitis, the mouse equivalent of MS.

A separate experiment showed all but 1 mouse model experienced a significant reversal of the disease 8 days after a single treatment with gene therapy.

Seven months later, the investigators found the treatment lasted and the mouse models that received gene therapy still showed no signs of disease, compared with the untreated mouse models that experienced neurological issues after 14 days.

The protein’s efficacy was further improved when combined with the drug rapamycin, which is used to coat heart stents and prevent organ transplant rejection.

Hoffman noted that they used rapamycin because it allows helpful regulatory T cells to proliferate while simultaneously blocking undesirable effector T cells.

Among the mouse models that received rapamycin and the gene therapy, 71% and 80% responded to treatment and went into near-complete remission by day 30. Contrastingly, the control mice relapsed in severe paralyzing or fatal experimental autoimmune encephalomyelitis disease.

The findings indicate that the combination treatment could be especially effective in stopping rapidly progressing paralysis, the authors noted.

“If we can provide long-term remission for people and a long-term quality of life, that is a very promising outcome,” Hoffman said.

Although the findings show promise, more research needs to be done using other preclinical models before the technique can be tested in human clinical trials. Furthermore, the investigators will also need to target the full suite of proteins that are implicated in MS.

“In summary, we have developed a novel immunotherapy that reverses debilitating paralysis in an animal model of MS that is superior to the traditional non-specific immunosuppression therapies currently available,” the authors concluded. “The application of this approach as a clinical therapy for treating MS and other human autoimmune diseases warrants further investigation.”