Patients with complex tuberous sclerosis, a genetic disorder characterized by the growth of noncancerous tumors in multiple organs of the body, have limited treatment options. A team led by researchers at Massachusetts General Hospital (MGH) has now shown that gene therapy can effectively treat mice that express one of the genes that cause the disease. The research is published in Advances in science.
The gene, called TSC2, encodes for tuberin, a protein that inhibits cell growth and proliferation. When mutations occur in TSC2, leading to tuberine deficiency in cells, the cells proliferate and proliferate, leading to the formation of tumors.
To restore TSC2 and tuberin function in a mouse model of tuberous sclerosis complex, researchers developed a type of gene therapy using an adeno-linked virus vector carrying the DNA encoding for form thickness of tuberin (corresponding to within the carrying capacity of the vector.) and functions as the normal full-term tuberin protein. Mice with tuberous sclerosis had a short duration of approximately 58 days on average, and showed signs of brain deficits consistent with those commonly seen in patients with the disease. When the mice were introduced intravenously with the gene therapy treatment, however, the average survival was extended to 462 days, and their brains showed less signs of damage.
Conventional treatments for tuberous sclerosis complications include surgery and / or lifelong treatment with drugs that cause immune suppression and potentially affect early brain development. Therefore, there is a clear need for other therapeutic methods to diagnose this disease. Adeno-associated virus vectors have been widely used in clinical trials for many hereditary diseases with minimal poisoning, long-term activity in nondividing cells, and improvement in symptoms. “
Shilpa Prabhakar, Associate Author, Researcher, MGH Departments of Neurology and Radiation
She notes that benefits can be seen after a single injection, and some forms of the viral vector can enter the brain and peripheral organs effectively after intravenous injection.
The U.S. Food and Drug Administration has approved a limited number of gene therapy products for use in humans, and the results of this study suggest the need for clinical trials to test the potential of the strategy in patients with complex tuberous sclerosis.
Source:
Massachusetts General Hospital
Magazine Reference:
Cheah, PS., et al. (2021) Gene therapy for type 2 tuberous sclerosis in a mouse model by delivering AAV9 encoding a thick form of tuberin. Advances in science. doi.org/10.1126/sciadv.abb1703.