New Study Links Metabolic Defects to Dravet Syndrome

New research is the first to identify defects related to metabolism (how the body processes and uses energy) in children with Dravet syndrome.

Dravet syndrome is a severe form of epilepsy, usually diagnosed in infancy, that is associated with developmental delays and severe seizures. It has long been recognized for its neurological symptoms, but its underlying metabolic issues, especially at the cellular level, have not been extensively explored until this study.

“It’s been proven that some children with Dravet syndrome respond to ketogenic diets, which suggests that energy metabolism is somehow involved in the condition. Our goal was to explore this connection further to gain a deeper understanding of its role in managing the syndrome,” said Manisha Patel, PhD, the paper’s senior author and Associate Dean for Research at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.

The pilot study looked at the blood-derived immune cells of eight children with Dravet syndrome with known mutations in their sodium channels. Researchers then compared them to age- and sex-matched control cells to explore whether the cells from children with the condition exhibit different energy metabolism characteristics.

In children with Dravet syndrome, the researchers found significant mitochondrial dysfunction in their immune cells. These cells had lower energy production, with particular problems in mitochondrial respiration. To compensate, the cells shifted towards using fatty acids for energy. Despite this, other aspects of the cells, such as glucose metabolism and mitochondrial structure, appeared normal.

This study suggests that mitochondrial defects play a role in the metabolic dysfunction observed in Dravet syndrome. These metabolic alterations could help explain the neurological symptoms of Dravet syndrome, like seizures and developmental delays, which require large amounts of energy in the brain.

“This opens the door for further research into the role of mitochondrial dysfunction in epilepsy and other neurological disorders. Understanding these defects could lead to new treatment options aimed at improving cellular energy production, potentially benefiting children and adults with Dravet syndrome or a similar condition,” adds Patel.

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