Gene therapy based on AAV virus vector is expected to treat tuberous sclerosis

Gene therapy based on AAV virus vector is expected to treat tuberous sclerosis. Tuberous sclerosis complex (tuberous sclerosis complex, TSC) is a hereditary disease characterized by the growth of non-cancerous tumors in multiple organs of the body, with limited treatment options for patients. In a new study, a team led by researchers from Massachusetts General Hospital (MGH) has now reported that gene therapy can effectively treat mice that express one of the mutant genes that cause the disease.

The relevant research results were published in the Journal of Science Advances on January 8, 2021, with the title of the paper “Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin”.

This gene is called TSC2, which encodes tuberin, a protein that inhibits cell growth and proliferation. When TSC2 is mutated and results in a lack of nodulin in the cell, the cell will expand and proliferate to form a tumor.

In order to restore the function of TSC2 and nodulin in a mouse tuberous sclerosis model, these researchers developed a form of gene therapy that uses an adeno-associated virus vector that carries DNA encoding a concentrated form of nodulin ( AAV), this condensed form of tuberin (cTuberin) functions like a normal full-length tuberin.

The average lifespan of mice with tuberous sclerosis is shortened by about 58 days, and the signs of brain abnormalities they show are consistent with the symptoms that patients with tuberous sclerosis often experience. However, when these mice were given gene therapy by intravenous injection, their average survival time was extended to 462 days, and their brains showed signs of reduced damage.

Shilpa Prabhakar, the co-first author of the paper and a researcher in the Department of Neurology of MGH, said, “Current treatments for tuberous sclerosis include surgery and/or lifelong medication. These drugs can cause immunosuppression and may impair early brain development.”

Prabhakar added, “AAV has been widely used in clinical trials for many hereditary diseases. It has almost no toxicity. It acts on non-dividing cells for a long time and improves symptoms.” She pointed out that the therapeutic benefits can be observed after a single injection. Some forms of viral vectors can effectively enter the brain and peripheral organs after intravenous injection.

The U.S. Food and Drug Administration (FDA) has approved a limited number of gene therapy products for human treatment. The results of this study indicate that clinical trials are necessary to test the potential of this strategy in the treatment of patients with tuberous sclerosis.

(source:internet, reference only)

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