Texas A&M neuroscientists discover new therapy for refractory epilepsy

Findings have clinical implications that could lead to eventual treatment of uncontrolled seizures
June 23, 2020

Epilepsy is a chronic neurological disorder characterized by unpredictable seizures that affects more than 65 million people in the world and more than 3 million adults in the United States alone. Every year, around 150,000 people develop epilepsy in the United States.

Seizures can usually be controlled with antiepileptic medications, which are the most common way to treat seizures. However, as many as two out of five patients with epilepsy have seizures that are refractory, meaning they are not controlled with current seizure medications, according to the Epilepsy Foundation.

More specifically, refractory epilepsy occurs when seizures are frequent enough, or the therapy is troublesome enough, to the point where it interferes with a person’s life. Current data suggests that many epilepsy patients could die due to uncontrolled or refractory seizures.

Scientists around the world have been on an active pursuit to better understand this condition and to identify a better way to block these refractory seizures with targeted therapies, including either new medicines or a combination of current medicines.

Samba Reddy, PhD, RPh, professor of neuroscience and experimental therapeutics at the Texas A&M College of Medicine, has been working for more than two decades to find solutions to this and other challenges in the epilepsy field. His lab has been conducting investigations on molecular mechanisms of seizures and translating the concepts into innovative therapies for curing epilepsy.

Reddy’s research has laid the groundwork for neurosteroids—powerful anticonvulsants—in brain disorders. The first neurosteroid (brexanolone) was approved by the Food and Drug Administration for clinical use in post-partum depression. Another neurosteroid, called ganaxolone, is in Phase 3 clinical trials for treating seizure disorder.

Reddy’s recent work, co-authored by his graduate student Shu-Hui Chuang, was published in the Journal of Pharmacology and Experimental Therapeutics, and it provides a practical approach to a better treatment of refractory seizures.

Reddy and Chuang utilized a gold-standard arithmetic technique called isobolographic analysis to select the best combination regimen of two drugs in order to achieve the highest efficacy. Through the isobolographic analysis, they found that the positive interaction between two neurosteroids (brexanolone and ganaxolone) and two antiepileptic medications (tiagabine and midazolam) is so significant that there is possibility it could help treat refractory epilepsy.

“Our study suggests the viability of launching neurosteroid combination therapy for epilepsy,” Reddy said. “A prospective clinical trial is needed to demonstrate overall clinical impact of this therapy, especially in adults and children with drug resistant epilepsy, but these findings for the first time provide a strong rationale for clinical use of neurosteroid plus tiagabine or neurosteroid plus midazolam for refractory seizures and other hyperexcitability conditions.”

Reddy hopes his findings will lead to a treatment of refractory seizures, and, in the long run, he hopes to find a cure for epilepsy.

“Epilepsy is one of the most complex brain disorders,” Reddy said. “There is some stigma associated with epilepsy. Imagine a patient having a seizure at a party, school or store. It’s a very difficult situation for them, and there is some part of discrimination that happens inherently. Most of what I am interested in is helping patients feel better.”

The U.S. CounterACT Program, Office of the Director, National Institutes of Health and the National Institute of Neurologic Disorders and Stroke have supported this research.

— Gracie Blackwell

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