Multiple Sclerosis (MS) halted by gene therapy

21 September 2017
Posted by Chris Smith.

A gene therapy technique that can halt the progression of a condition resembling multiple sclerosis (MS) in mice has been unveiled by researchers in the US.

More than two million people are living with MS worldwide, with women affected up to three times more frequently than men, and inhabitants at high latitudes at particular risk. The condition occurs when the immune system attacks the substance myelin, which encases and shields nerve fibres in the brain and spinal cord. Repeated immune assaults destroy progressively more myelin, disrupting the transmission of nerve signals and producing worsening disability, which can include difficulty in moving, numbness and sensory disturbance, and sight loss if the optic nerves are affected.

The mainstay of current therapy is immune suppression, the rationale being to try to reduce the activity of the immune T lymphocytes that are causing the disease. The normal role of immune T cells is to attack virally-infected cells or foreign tissue, but for reasons that doctors do not yet understand, a breakaway rogue contingent of these cells emerges. Known as autoreactive T cells, these immune killers regard a person's own myelin tissue as hostile, and they mount a relentless attack on the nervous system.

Immunosuppressing a person can therefore be only a temporary measure. Not only does it mere;y defer the inevitable, it also leaves the patient vulnerable to infections, the side effects of the drugs themselves, and at increased risk of cancer.

Now a team at the University of Florida, led by Brad Hoffman, have published - and patented - a gene-therapy-based technique that can reprogramme the immune system and halt inflammation of the type that causes MS.

Their approach has been to use a modified, harmless virus called an AAV (adeno-associated virus) to trigger the expression within the liver of a marker called MOG that is present in normal myelin.  MOG stands for "myelin oligodendrocyte glycoprotein" and is one of the proteins responsible for the correct function of myelin in the nervous system. It's also one of the molecules targeted inappropriately by the immune system in MS patients.

But displaying it temporarily in the liver instead triggers a immune response known as "tolerance". A different family of immune cells, called regulatory T cells (Tregs), are recruited and proliferate. These cells have a powerful damping effect on the toxic T cells trying to attack the nervous system. And if mice with the rodent equivalent of MS (a condition called EAE - experimental autoimmune encephalomyelitis), are triggered to produce these cells by administering a dose of the MOG-carrying virus, their disease halts, the symptoms improve dramatically, the animals remain well subsequently and, critically, do not relapse.

The researchers were able to show that, in response to the therapy, the mice produce Tregs capable of suppressing the action of the animals' autoreactive T cells. In the culture dish, Tregs collected from these mice prevented T cells from reacting to myelin. Encouragingly, the animals showed no side effects or signs of liver damage in response to the therapy. 

Hoffman is encouraged and enthusiastic about the results, but nevertheless cautious. "These are mice, and this is just a model of how MS behaves in a human. We don't want to give people false hope. But, we think we could use this approach to go in early and halt the progression of MS in patients recently diagnosed with MS and make a big difference to the outcome for them..."

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