New Gene Therapy Could Reverse Paralysis in Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune disease in the central nervous system that affects the brain and spinal cord. When someone has MS, their immune system thinks that myelin is a foreign body and begins attacking the protective sheath. Myelin is the protective sheath that surrounds the nerve fibers in the central nervous system. These nerve fibers transmit messages from the brain and to the body and vice versa. In MS, the damaged myelin sheath can leave nerve fibers exposed with plaques and lesions. The disruption in the myelin sheath can cause a disruption in the flow of messages between the brain and body leading to increasing disability.

A new gene therapy has been discovered that can reverse the degenerative effects of MS. for this the adeno-associated virus immunotherapy can have lot of potential. This therapy works by producing inside the body MOG-specific regulatory T cells. In patients with MS they seem to store the immune response. These T-regulatory cells are referred to as Tregs. In immune tolerance it plays a critical role. The function of effector CD4+ is suppressed by Tregs. In controlling and mediating autoimmune response CD4+ plays an important role. In one research through the transfer of polyclonal CD4+CD25+ Tregs, researchers were able to reduce or prevent the effects of encephalomyelitis. In developing an immune-regulatory therapy, the challenges remain robust and sustainable.

By using pre clinical mouse models the researchers were able to develop in-vivo gene therapy. A gene transfer vector was designed. This vector would allow inside the liver cells expression of full-length myelin oligodendrocyte glycoprotein by targeting the liver. A production of MOG-specific Tregs is caused by this novel gene immune therapy. In patients with MS this would restore the immune response.

Also by using this therapy it was possible to produce and expand antigen-specific FOXP3+Tregs.  Group of mice were taken who has mild to moderate neurological deficits of MS. these mice were given gene therapy. There was an improvement and protection from EAE. Also the pathological and clinical signs of MS could be reversed by the vector therapy. Also by using a short course of AAV therapy and immunosuppressant’s, it was possible to protect the mice from the end-stage fatal EAE. Also after severe paralysis it was possible to restore mobility and function. According to researchers after a short course of immunosuppressant drug, researchers were able to prove the effectiveness of AAV therapy. This would prevent and debilitate the MS symptoms. however, for the therapy to be active, it should be administered in the early stage of the disease. this therapy can point out in being effective for other autoimmune diseases.

Researchers were very happy about the results of the study. They were surprised with the duration of reversal and the magnitude and level of response. Worldwide MS affects 2.3 million people. It is thought to occur since the self-reactive effector T cells become active. Inside the myelin sheath that surrounds the nerve cells there is an attack of proteins. While normally Tregs prevents self-destructive activity but somehow regulation is escaped by these rogue cells and they destroy the myelin sheath.

To deliver curative or therapeutic protein, researchers have focussed on using gene therapy. But this time to explore and exploit the natural ability of liver to induce immune tolerance, researchers used gene therapy. They delivered the gene into the myelin sheath protein by using the AAV vector. They also added the production of MOG in liver. By expression of MOG, by the liver cells the immune system can be triggered. This causes production of highly specific Tregs. The autoreactive effector T cells are prevented from attacking the protein in the myelin sheath. 

The mice that were given AAV vector did not show any signs of distress or neurological disability. Thus it was concluded that no deleterious immune response is provoked by hepatocyte expression of MOG.