Future of epilepsy treatment depends on overcoming obstacles to gene-targeting therapy

ORLANDO — While effective medications for epilepsy exist, scientific advancement requires that future gene-targeting therapies or cures benefit the largest number of patients while overcoming several barriers, according to a presentation.

“I like to think we’ve moved into what I call a ‘gene matching era,’” Gemma Carvill, PhD, assistant professor of neurology at Northwestern Feinberg School of Medicine, told attendees at the American Epilepsy Society annual meeting. “With this progress in terms of the identification of the genes that cause epilepsy ... we know the largest cause of these disorders is through monogenic causes.”

Over the last 30 years, the evolution of genetic studies with respect to epilepsy have migrated to the point that researchers can pinpoint which genetic factors influence which types of the condition, Carvill said. Focal epilepsy, which accounts for the greatest number of cases, rarely has a monogenic cause with approximately 16% heritability, while genetic generalized epilepsy has 40% heritability with rare monogenic causes and developmental/epileptic encephalopathy is mostly monogenic but accounts for 1 out of every 2000 cases.

Nonetheless, the path from treatment to cure still encounters a web of intricate issues to overcome, Carvill noted. The first issue is when to treat the individual, as the timing of the condition’s initial appearance is often unknown, ranging from childhood to adulthood, along with the type and dosage of medication. Replicating the condition in animal and cellular models presents another challenge, as animal models often cannot recapitulate human phenotypes and attempting to use stem cells to reproduce conditions where epilepsy comes to the fore are too variable to draw accurate conclusions. Carvill also stated that a delivery method for treatments encounters issues with both non-integrative and integrative solutions owing to the need for repeat dosing or treatment-emergent adverse events.

Additionally, potential novel treatments require specifically designed clinical trials for maximum benefit with clear outcome measures and endpoints to benefit the maximum number of patients. Too often, Carvill said, precision therapies end up benefiting a smaller number of patients, necessitating research and development into more therapies.

As with other specialties, effective treatments and eventual cures for epilepsy require an effort to provide more equitable access, she added.

“Despite the challenges, I think we have a lot of opportunities for targeting genes,” Carvill said. “We can treat the cause but not the symptoms and be a cure and not a treatment.”