Gene Therapy for Monogenic Encephalopathies

"Gene therapy could lastingly improve the lives of patients with monogenic diseases such as Dravet Syndrome."


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.

Dr. Rubén Hernández Alcoceba


   +34 948 194 700 | Ext. 81 4032
   Research profile

Objectives of our research

Correction of RNAs

Design and evaluation of sequences that allow the correction of messenger RNAs by trans-complementation.

Therapeutic sequences

Incorporation of therapeutic sequences into brain-targeted gene therapy vectors.


Evaluation of safety and therapeutic effect in animal models of the disease.

Lines of research

Based on the proof of concept performed with adenoviral vectors, we are investigating alternative methods that allow a more homogeneous gene transfer in the brain, and a physiologically patterned expression of therapeutic genes. Therefore, we are currently developing trans-complementation techniques using vectors derived from adeno-associated viruses (AAV).


Our research has demonstrated that the transfer of the complete coding sequence for the SCN1A gene has a positive biological effect in a mouse model of Dravet syndrome. Specifically, it increased survival and decreased the severity of several pathological manifestations already established, such as sensitivity to epileptic seizures caused by hyperthermia or motor disturbances. This effect was observed in adolescent mice treated with adenoviral vectors.

Our group continues to optimize methods for introducing therapeutic genes into the brain, adapting them for safe and effective clinical implementation in the shortest possible time. To this end, we work in collaboration with the neuropediatrics service and the Dravet unit at the CUN.

Scientific activity of the Gene Therapy Group
of Congenital Diseases with Neurological Affect