First of its Kind Study Identifies Metabolic Defects in Dravet Syndrome
Featuring the work of Kelly Knupp & Manisha Patel, CURE Epilepsy Grantee. Article published by University of Colorado Anschutz Medical Campus.
Recent research has identified defects related to metabolism in children with Dravet syndrome. Dravet syndrome is a severe form of epilepsy 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,” said Manisha Patel, PhD, associate dean for research at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.
In the pilot study, her team used blood-derived immune cells from eight children with Dravet syndrome to create lymphoblast cell lines (LCLs). The team then compared these LCLs to age- and sex-matched control LCLs to explore whether the cells from children with the condition exhibit different energy metabolism characteristics.
“By using the LCLs, we’re able to look at patients with a variety of mutations in a non-invasive way. This gets us closer to a full picture of what’s happening in their bodies and phenotype that may be causing their seizures and severe symptoms,” said co-author Kelly Knupp, MD.
The researchers found significant mitochondrial dysfunction in the LCLs of children with Dravet syndrome. These cells had lower energy production, with particular problems in mitochondrial respiration. To compensate, the cells shifted toward using fatty acids for energy.
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,” Patel said.