Cook Children’s Neurosciences Research Center receives grant to study biomarkers of Dravet syndrome
Christos Papadelis, Ph.D., founding director of the Neurosciences Research Center at the Jane and John Justin Institute for Mind Health at Cook Children's, received a research grant from Encoded Therapeutics, a pharmaceutical company that develops precision gene therapies for a broad range of severe genetic disorders. The grant of nearly $500,000 will help fund Dr. Papadelis' research on developing novel electrophysiological biomarkers of g-aminobutyric acid (GABA) metabolism in children with Dravet syndrome.
Dravet syndrome is a rare genetic disorder. It causes a catastrophic form of epilepsy with prolonged seizures that are often unprovoked or triggered by elevated temperature and fever. For these children, seizures are difficult to control with anti-seizure medications. In addition to devastating seizures, children with Dravet syndrome often suffer from loss of motor skills, intellectual disability, speech impairment and difficulty with movement. Dravet syndrome most often is caused by variants in the SCN1a gene that encodes an important sodium channel involved in GABA inhibition, though not all SCN1a variants result in this condition. Biomarkers allowing for early identification of Dravet syndrome and initiation of appropriate treatment are essential to improving outcomes and measuring effectiveness of therapy.
Previous research in Dravet syndrome indicates an abnormal pathophysiological mechanism of GABA neurotransmitter, a chemical messenger in the brain, which slows down brain activity by blocking specific signals. This deficit may disrupt the balance between excitatory and inhibitory brain signals leading to devastating seizures. Currently, there are no reliable biomarkers for assessing the levels of GABA in the human brain. The lack of biomarkers impedes the development of treatments that regulate GABA metabolism in children with Dravet syndrome and other genetic disorders.
Dr. Papadelis proposes the use of noninvasive techniques that measure the electric and magnetic activity generated by the human brain, such as the high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG), as biomarkers for monitoring the levels of GABA in the brain. These techniques would allow measurement of high-frequency oscillatory brain activity that correlates with the levels of GABA neurotransmitter. Developing such a biomarker is critical for understanding the pathophysiological mechanism of GABA metabolism in children with Dravet syndrome. This development potentially will guide the future of GABAergic modulation treatments, which will enable medical practitioners to not only treat the seizures in children with Dravet syndrome, but also improve their quality of life.
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