Gene Therapy Reverses the Tide of Multiple Sclerosis in Mice


A new technique that delivers gene-specific instructions inside the body can prevent — and even fully reverse — multiple sclerosis in mouse models.

The breakthrough animal study, which may hold significant implications for humans, employs a novel form of gene therapy to reinforce the protective barrier of nerve cells in the brain and spinal cord and limit or reverse destruction of the barrier, which is known as the myelin sheath.

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In cases of multiple sclerosis, a degenerative condition that affects some 2.3 million people worldwide, the body’s T cells destroy the myelin sheath, exposing nerve cells to prolonged and irreversible damage. Common symptoms of multiple sclerosis include cognitive problems, muscle weakness, problems with coordination and balance and even paralysis.

But the targeted approach, combining cutting-edge gene therapy with a currently available medication, resulted in a “near-complete remission” among animals studied, according to the researchers.

“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 disease,” said senior study author Brad Hoffman, an assistant professor in the departments of pediatrics and neuroscience at the University of Florida College of Medicine.

“In contrast, most current therapies for autoimmune diseases such as multiple sclerosis are based on general immune suppression, which has various side effects or complications,” said Hoffman.

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Instead of a generalized approach to immune suppression, the new technique uses a virus to deliver a specific gene to the animals’ livers. That gene acts to build up a durable myelin sheath that can withstand the body’s attack via T cells and thereby render the autoimmune disorder something of a negligible condition.

The virus the research team tapped into is an adeno-associated virus (AAV) vector, which delivered the myelin-boosting genes directly to the animals’ livers. The researchers report that the direct-to-liver application caused regular T cells to go into overdrive, suppressing the harmful T cells that are associated with the condition.

“Traditional AAV gene therapy has been focused on delivering a transgene that produces a therapeutic protein,” Hoffman says. “Here we use the platform purposely to induce specific regulatory cells in order to restore immune tolerance and reverse an autoimmune disease,” said Hoffman.

Related: Gene Therapy Used to Cure Boy of Sickle Cell Disease

Among the animals studied, up to 80 percent of them went into virtually complete remission of the condition even after experiencing paralysis in their hind limbs. The new approach, which will require further testing in animal studies before it can move to human trials, has the researchers optimistic that a new-line therapy is on the horizon.

“Our results are very promising. We have demonstrated that stable immune tolerance can be re-established and that active disease can be stopped and clinical symptoms reversed using our gene immunotherapy, especially during early onset of disease,” Hoffman says. “Even though these studies were performed in a less complex mouse model, the data suggest this may be a potential therapy in humans with additional optimization.”

Ultimately, the potential benefits behind the gene therapy are substantial.

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