MS Gene Therapy Shows Good Results in Mice, but Human Trials Remain Distant

Researchers have taken the first steps towards the development of a gene therapy for multiple sclerosis — a treatment that boosted anti-inflammatory immune processes and reversed severe paralysis in mouse models of the disease.

The University of Florida Health research team said it was optimistic that the therapy can work in humans. But plenty of work remains before the experimental treatment can be tested in clinical trials.

The secret to the successful experiments was an approach involving the liver — an organ not usually associated with MS. The study, “Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis,” showed that the organ has the potential to stop a harmful immune response.

To make the liver start these protective processes, researchers transferred myelin oligodendrocyte glycoprotein (MOG) — a component of brain myelin — into liver cells. Myelin is the protective coating around nerve cells whose loss is associated with MS.

The team’s report, published in the journal Molecular Therapy, showed that the protein’s presence in the liver triggered the production of MOG-specific regulatory T-cells, or Tregs. These Tregs have the potential to stop an immune attack targeting the protein, the team demonstrated in a set of experiments in lab dishes.

“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,” Brad E. Hoffman, an assistant professor in the departments of pediatrics and neuroscience at the University of Florida College of Medicine, said in a press release.

Researchers first used the gene therapy — composed of a harmless virus that delivers the gene into liver cells — on its own in mice. The animals were exposed to the MOG protein in a way that usually leads to experimental autoimmune encephalomyelitis (EAE), a mouse version of MS.

Animals that had been treated with the gene therapy did not develop the disease. They also had higher numbers of Tregs in their blood. This supported the notion that the therapy works by harnessing the tolerogenic mechanisms that prevent an immune response.

Much more importantly, the therapy could reverse disease, the researchers discovered. The treatment even improved walking ability in mice with severe paralysis of their hind legs. Tests in earlier disease stages showed equally good results.

The effects were also durable, researchers said. Treated animals lived for seven months without showing signs of disease, while all the control mice had neurological problems after two weeks.

When the team combined the gene therapy with a drug called rapamycin, which is already used to suppress immune response, the effect was even more potent. While the gene therapy alone reduced the disease severity in the paralyzed mice, the combination allowed all but one mouse to completely regain their functions.

To illustrate the radical impact of the treatment, researchers have posted a video of the treated and control mice.

Before the treatment can be tested on patients, researchers said they need to know more about the detailed mechanisms of its action.

Still, Hoffman and his team believe the approach has the potential to make a difference in patients’ lives.

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