After 20-plus years of research and development, a breakthrough medication treating patients suffering from epilepsy has finally hit the market. Ganaxolone, a synthetic analog of allopregnanolone, is a broad-spectrum anti-seizure drug with a unique mode of action in the brain that contributes to its robust efficacy in treating epileptic seizures, including difficult-to-treat seizures in rare and genetic epilepsies.
Dr. Samba Reddy, a Regents Professor of Neuroscience and Experimental Therapeutics, and the founding Director of Texas A&M Institute of Pharmacology and Neurotherapeutics, was happy to receive the FDA approval in March 2022. His research contributed to the development of this brain medicine, which is the only one approved by the FDA for this condition.
Reddy’s work laid the foundation for neurosteroids in epilepsy. He was the first to discover ganaxolone’s efficacy in refractory seizures and identified its molecular mechanism including its ability to activate both synaptic and extrasynaptic GABA-A receptors in the brain.
Reddy began his research on ganaxolone in 1999 with an interest in epilepsy in women, finding that medication-resistant epilepsy occurs in ~30% of patients with epilepsy; about one million patients experience seizures that are unable to be controlled by medicine.
Epilepsy affects 3.4 million adults and children in the United States, and many experience high rates of body injuries, morbidity, or mortality from repeated seizures.
“The goal of preventing seizures is suboptimal with current medicines,” Reddy said. “Pediatric seizures and rare infantile epileptic diseases are conditions for which medical needs are not fully met. Such epilepsy typically requires trials of therapy with new medicines with a unique mode of action, such as neurosteroids. I had a strong belief that these compounds called neurosteroids would have strong potential because they already exist in the brain.”
The neurosteroid ganaxolone is the first FDA-approved drug to treat seizures for CDLK5 deficiency disorder (CDD) in children. CDD is a rare developmental epileptic syndrome caused by mutations in the CDKL5 gene, which is responsible for making proteins that are important for normal brain functioning and development. Children with this condition suffer from infantile-onset epilepsy which responds poorly to current therapies.
“The FDA approval of ganaxolone validates the life-long science that I’ve dedicated myself to,” Reddy said. “The most gratifying thing is to see the research that we’ve done translate to patient-care. This approval will give a boost to furthering development of neurosteroids and specific therapies to dramatically improve epilepsy outcomes.”
Reddy hopes to see his research extend to patients with an array of brain injuries and complications.
Reddy’s 22 years of research on neurosteroids have been conducted at three institutions (NIH, NC State, and Texas A&M). Most of this work was supported by funds from the U.S. National Institutes of Health and internal support.