The medical director of the Comprehensive Epilepsy Clinic at Nicklaus Children’s Hospital discusses his early stage gene therapy trial for Dravet syndrome.
“Before the natural history of the patient has declared itself, you really don't know whether they will have Dravet syndrome or a severity thats somewhere else on the GEFS+ spectrum.”
Loss of function mutations in the SCN1A gene often result in various seizure disorders, most commonly Dravet syndrome, in which nearly 90% of patients have a mutation on the gene.
Given the success of gene therapies in other neurologic disorders, such as spinal muscular atrophy, researchers believe that a modified approach may also hold promise for SCN1A-positive epilepsies. At the 2019 American Epilepsy Society Annual Meeting, Ian Miller, MD, medical director of the Comprehensive Epilepsy Clinic at Nicklaus Children’s Hospital, and colleagues, presented a novel approach to adeno-associated viral vector-based gene therapy for SCN1A-positive epilepsy.
Miller detailed how one of the challenges with current gene therapy approaches is that the viral vectors can only accommodate small genes, not large, complex ones like SCN1A. Instead, Miller and colleagues approach targets vector expression to GABAergic interneurons and upregulates endogenous SCN1A expression. Results from a mouse model study of Dravet syndrome showed that the engineered viral vector dramatically reduced hyperthermic and spontaneous seizures.
To learn more about the new approach, Miller sat down with NeurologyLive at AES 2019.
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