Researching Dravet Syndrome Biomarkers to Advance Treatment: Christos Papadelis, PhD

WATCH TIME: 6 minutes

"We hope that these methods and the biomarkers we develop will help us to assess the effectiveness of treatments that regulate the levels of GABA in the brain of [these pediatric patients] and help us develop new therapies for them."

Dravet syndrome (DS), a rare genetic disorder, causes a catastrophic form of epilepsy with prolonged seizures that are often unprovoked or triggered by elevated temperature and fever. The condition is most often caused by variants in the SCN1a gene that encodes an important sodium channel involved in g-aminobutyric acid (GABA) inhibition, though not all these variants result in DS. Biomarkers that allow early identification of DS and initiation of appropriate treatment may be critical for enhancing outcomes and measuring effectiveness of therapies.

Prior research in DS revealed an abnormal pathophysiological mechanism of GABA neurotransmitter, which is a chemical messenger in the brain, that can slow down brain activity by blocking out certain signals.¹ This deficit may potentially disrupt the balance between excitatory and inhibitory brain signals that lead to onset of seizures. Currently, there is a lack of reliable biomarkers for assessing the levels of GABA in the human brain which can impede the development of treatments.

In October 2022, Christos Papadelis, PhD, founding director of the Neurosciences Research Center at the Jane and John Justin Institute at Cook Children's Health Care System, received a research grant of nearly $500,000 from Encoded Therapeutics to help fund a study (NCT05651204) on developing novel electrophysiological biomarkers of GABA metabolism in pediatric patients with DS.¹ Papadelisrecently sat down with NeurologyLive^® in an interview to further discuss the role of the GABAergic system in the brain, and its significance in DS. He also spoke about how noninvasive techniques can help improve the assessment of brain activity in DS and the importance of researching biomarkers early in the life of patients with DS.

REFERENCES
1. Cook Children’s Neurosciences Research Center receives grant to study biomarkers of Dravet syndrome. News Release. Cook Children’s. October 11, 2022. Accessed May 24, 2024. https://www.arcuate.org/cook-childrens-neurosciences-research-center-receives-grant-to-study-biomarkers-of-dravet-syndrome/