Gene Therapy-Immunotherapy Combination Could Reverse Multiple Sclerosis

Multiple sclerosis (MS) was prevented and, in some cases, reversed in mouse models of the disease using an investigational gene therapy technique that suppresses the immune response that causes the disease, according to a study published by Molecular Therapy.

The study authors combined the transfer of a brain protein gene plus rapamycin, which essentially cured animal models of MS. These results suggest that curing humans of MS and other autoimmune disorders may be possible through the gene therapy-immunotherapy approach, according to the authors.

MS affects millions of people worldwide and is characterized by an immune attack against the myelin that protects nerves. Patients may experience issues with muscle strength, vision, and speech.

In the study, the authors delivered the myelin oligodendrocyte glycoprotein (MOG) into the livers of mice by using the adeno-associated virus (AAV). The MOG protein produces regulatory T cells, which can suppress the immune system attack against the myelin, according to the authors.

The efficacy of the gene therapy is due to the delivery of the protein to the liver, which promotes immune tolerance, according to the study.

“Using a clinically tested gene therapy platform, we are able to induce very specific regulatory T cells that target the self-reactive cells responsible for causing multiple sclerosis,” said researcher Brad E. Hoffman, PhD.

Many previous studies have shown that the MOG protein can prevent and reverse MS alone. In the current study, this approach was tested in groups of up to 10 mice and was conducted multiple times.

The authors found that the treatment was long-lasting. Mice treated with gene therapy alone were observed to have no signs of disease activity after 7 months, while control mice showed neurological problems within 14 days, according to the study.

When the gene therapy was combined with rapamycin, the efficacy of the treatment was amplified. Rapamycin is an immunotherapy drug used to prevent organ transplant rejections by dampening the immune response. The authors chose this drug because it allows regulatory T cells to proliferate and blocks effector T cells, according to the study.

Approximately 71% and 80% of the mice in the 2 groups administered the dual therapy went into near-complete remission. Remarkably, these mice previously had hind-limb paralysis or near quadriplegia.

These findings suggest that gene therapy plus rapamycin may be able to inhibit and reverse MS-related paralysis, according to the study.

The authors said that this approach must be studied further before being tested in humans, but the gene therapy-immunotherapy could possibly cure MS.

“If our gene immunotherapy can provide long-term disease remission, patients will have long-term improvement with a higher quality of life and that is a very promising outcome,” Dr Hoffman concluded.