Gene therapy reverses multiple sclerosis in mice

A novel gene therapy can reverse the symptoms and progression of disease in a mouse model of multiple sclerosis (MS).

The neurodegenerative illness is caused by the body's own immune system degrading and destroying nerve cells. US researchers have used a gene therapy approach in the livers of affected mice to produce more regulatory T-cells and reduce this autoimmune response.

'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 Dr Brad Hoffman at the University of Florida, College of Medicine in Gainesville, who led the study. 'Most current therapies for autoimmune diseases such as multiple sclerosis are based on general immune suppression, which has various side effects or complications.'

In MS, immune cells known as effector T-cells are thought to destroy myelin - the fatty sheath that protects nerve fibres. The study, published in Molecular Therapy, harnessed regulatory T-cells to reduce this behaviour. This approach has been shown to be safe and effective in patients with other autoimmune disorders such as type 1 diabetes, but the results are often insufficiently potent and short-lived.

To combat this issue, the researchers developed a strategy that utilised the liver's natural ability to induce immune tolerance. They injected the gene for a protein called myelin oligodendrocyte glycoprotein into the livers of mice, using a harmless virus vector; this then triggered the long-term production of regulatory T-cells.

Over seven months, symptoms were reversed in those mice that had already developed mild-to-moderate neurological deficits, and mobility restored in those with more severe symptoms such as hind-leg paralysis; by contrast, untreated mice developed neurological problems after 14 days.

'It's a very strong and potent result that we get from that treatment,' Dr Hoffman told The Gainesville Sun newspaper.

The gene therapy system alone did not fully reverse end-stage disease, however, but when combined with the immunosuppressive drug rapamycin, which allows the regulatory T-cells to proliferate, there was complete remission in the majority of the mice. And effects were long-lasting, with the mice protected from symptoms approximately 100 days later.

Though Dr Hoffman is optimistic about the potential of this approach in treating MS in humans, he cautions: 'This is done in a mouse model, and we always have to take that with a grain of salt.'

'This is a thorough and well-controlled set of experiments,' said Dr Gillies O'Bryan-Tear, from the Faculty of Pharmaceutical Medicine of the Royal College of Physicians of the United Kingdom, London. He noted that the study 'adds to the growing excitement being generated in the field of gene therapy'.