Metabolic aspects of genetic ion channel epilepsies

There is increasing awareness of contributions of impaired brain metabolism to epilepsies. We review existing studies regarding metabolism in epilepsies caused by mutations in sodium (SCN1A) and potassium (KCNA1) channels. This is important as gene therapy is not yet available. While there are still little data about impairments of brain metabolism, the studies revealed ketogenic diets to be mostly effective, particularly for Dravet syndrome with identified SCN1A mutations as well as mouse and zebrafish models with SCN1A and KCNA1 mutations. We discuss how ketogenic diet and potentially other metabolic therapies may help to prevent seizures in these ion channel epilepsies. AbstractNowadays, particularly in countries with high incomes, individual mutations in people affected by genetic epilepsies are identified, and genetic therapies are being developed. In addition, drugs are being screened to directly target specific mutations, and personalised medicine is possible. However, people with epilepsy do not yet benefit from these advances, and many types of epilepsies are medication-resistant, including Dravet syndrome. Thus, in the meantime, alternative and effective treatment options are needed. There is increasing evidence that metabolic deficits contribute to epileptic seizures and that such metabolic impairments may be amenable to treatment, with metabolic treatment options like the ketogenic diet being employed with some success. However, the brain metabolic alterations tha...

Source: Journal of Neurochemistry - August 18, 2023 Category: Neuroscience Authors: Elliott S. Neal, Weizhi Xu, Karin Borges Tags: REVIEW Source Type: research