Gene Therapy for Monogenic Encephalopathies

Brain diseases of genetic origin lack satisfactory treatments and cause serious deterioration in the quality of life of patients. In many cases they are due to mutations of a single gene, which alters the function of neurons without cell death being the primary cause of the clinical manifestations. Therefore, gene therapy performed in early stages offers the possibility of reversing the pathological process and avoiding progressive brain deterioration. Epileptic encephalopathies are the most frequent in this category, Dravet syndrome being one of the most representative examples. It affects 1 in 15,000 births and is characterized by frequent epileptic seizures, often prolonged and resistant to pharmacological treatment. Shortly after the onset of seizures, cognitive, motor and behavioral disturbances appear, severely altering the quality of life of patients and their families.

In the group we investigate various methods to restore the function of mutated genes in the brain, using Dravet syndrome caused by mutations in the SCN1A gene as a model. We develop strategies that use messenger RNA as a template for therapeutic molecules, thus avoiding potential problems arising from overexpression or in inappropriate cells. These methods can be adapted for the treatment of other genetic encephalopathies.