Hepatic gene therapy reverses disease in multiple sclerosis mouse model

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A research study has yielded pre-clinical evidence to support the feasibility of treating multiple sclerosis (MS) using liver-targeting gene transfer of myelin oligodendrocyte glycoprotein (MOG).

MS is an acquired autoimmune disease of the central nervous system (CNS), resulting in axon loss and myelin damage with focal T lymphocytic infiltration. MS is thought to result from activation of myelin-reactive CD4+ effector T cells, suppression of which by regulatory T cells (Tregs) have been shown effective in controlling the disease in mice models.

However, the lack of large-scale antigen-specific Treg expansion techniques remain a bottleneck for clinical use of Treg immunotherapy in treating MS. An alternative and efficient in vivo approach for inducing antigen-specific tolerance is through ectopic expression of an antigen in the liver. By utilizing this tolerogenic property of the liver, authors of the present study induced robust antigen-specific immune tolerance and thus reversed disease symptoms in an MS mouse model.

In the study published in Molecular Therapy, researchers the University of Florida used adeno-associated virus (AAV) to design a liver-targeting gene transfer vector that expresses full-length MOG, a neuroprotein in hepatocytes. MS mice were systemically injected with a single dose of the transgenic vector and results showed that AAV-mediated immunotherapy reduced CNS inflammation and significantly reversed clinical symptoms of the disease in these mice.

Thus, the study provides preclinical evidence to support the potential of using AAV-mediated Treg therapy in inducing antigen-specific immune tolerance for treating MS and other autoimmune disorders.

Source: Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis; DOI