Interneuron-specific gene replacement therapy for Dravet Syndrome: Preclinical Developments

Dr. Franck Kalume is an associate professor of Neurological Surgery at the University of Washington.

Dr. Franck Kalume’s upcoming seminar will highlight a major breakthrough in AAV-based gene therapy for Dravet syndrome (DS), a severe and debilitating childhood epilepsy disorder. He recently led a collaborative study with researchers from Seattle Children’s and the Allen Institute that resulted in the development of a promising interneuron-specific dual-AAV gene replacement strategy for DS. The team demonstrated that this approach successfully restored SCN1A function and rescued epileptic phenotypes in mouse models of the disease.
To this end, the researchers employed split-intein technology combined with a dual-vector delivery system to overcome the size constraints of the SCN1A gene. To target expression of functional NaV1.1 channels specifically in GABAergic interneurons, the DLX2.0 enhancer was used. This innovative strategy led to complete protection against premature death and a significant reduction in seizures, with durable therapeutic effects and no detectable off-target activity or toxicity.
During the seminar, Dr. Kalume will guide the audience through the design, execution, and broader implications of this cutting-edge research. The findings not only represent a transformative step toward a curative treatment for DS but also establish a new paradigm for precision-targeted AAV therapies in other monogenic neurological disorders.

Learn more

Hosted by MacKenzie Howard

To subscribe to our Seminars Series mailing list, please visit https://utlists.utexas.edu/sympa/info/neu-seminars and click on "Subscribe" in the left-hand column.  

Please contact Neuro.Seminar.Series@austin.utexas.edu with any questions.