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Faculty Profile: UVA Associate Professor of Anesthesiology, Manoj Patel, Ph.D.

According to the American Epilepsy Society, one in 26 Americans will develop epilepsy in their lifetime. The fourth most common neurological disease, epilepsy predisposes a person to recurrent unprovoked seizures and is a major public health concern around the world.

Manoj Patel, Associate Professor of Anesthesiology, is an electrophysiologist who has been studying seizures at UVA for almost two decades. Seizures occur when there is an over-activity of electrical discharges in brain neurons. Sodium channels play a major role for controlling the electrical discharges, known as action potentials. Humans express nine different sodium channels, each with a unique function. The human brain expresses four different types of sodium channels that have become important targets in treating a number of neurological disorders. 

Anticonvulsants (AEDs) are used to control excessive brain discharges in epilepsy. Drug therapies on the market today broadly target all sodium channels, including ones functioning normally. As a result, a disproportionate number of epilepsy patients continue to experience seizures or severe adverse side effects while taking anticonvulsants. Limitations in the available therapies elucidate the need for more effective and safer antiepileptic medications.

Patel is in the process of designing and testing small molecule compounds that have the potential to become a marketable drug therapy for epilepsy and are designed to target and suppress over-activity in a specific neuronal sodium channel isoform known as Nav1.6, encoded by the gene SCN8A. For nearly a decade, Patel has been collaborating with Mirko Rivara, a medicinal chemist in the Department of Pharmacy at the University of Parma in Italy to develop and test the compound.

Since the first pediatric epilepsy patient with a mutation in the SCN8A channel was identified in 2012, the mutation was added to the general screening test for epilepsy, and cases are continuously reported. The discovery of this mutation shaped the development of successive generations of compounds, and identified a clear path forward for Patel and Rivara.

Pediatric patients with mutations in SCN8A can be diagnosed as early as four months old and make up a specific subset of epilepsy patients. A child who took their first steps, or said their first words who has a seizure can experience significant developmental setbacks after the episode, reversing any developmental progress. The disease is devastating in pediatric patients; almost all have different degrees of motor dysfunction or intellectual disability, and life expectancy rarely exceeds the teenage years. For parents of a child with epilepsy, the work that Patel is conducting at UVA to develop a selective blocker is their only hope.

“Even if we aren’t successful in making a selective blocker, making one that is safer than what is currently on the market would also be a significant achievement,” Patel said. “The side effects of clinically available anticonvulsants can be severe in adult and especially pediatric patients.”

Pharmaceutical companies have shied away from pursuing research in this area, as it’s seen as add-on therapy to existing anticonvulsants on the market. The opportunity to pursue drug development and eventual commercialization would come from a licensing agreement with a biotechnology company or by launching a new venture.

After Patel presented his research on the original compounds to a faculty peer group, Dean Wilkes of the UVA School of Medicine encouraged him to engage with LVG to ensure his research was properly protected. A missed opportunity to patent the original compounds prompted Patel to establish a relationship with LVG to pursue a provisional patent on the secondary iteration of the compounds.

Since his first invention disclosure in 2014, LVG has guided him through the patent process and has filed a provisional patent application that converted in 2018. LVG has built a rapport with Patel, advising him to pursue funding from the Ivy Foundation, which supports biomedical innovation and translational research projects at UVA, and making industry introductions for him to present his research to biotech companies and potential licensees of his compound.

“Our goal is to start a company to further develop these compounds into a drug to treat the small children who suffer from this disease,” says Patel. “As a scientist, I have limited business knowledge, so to have access to the resources and expertise at LVG will be crucial for the commercialization of the compound.”

The licensing team at LVG will continue to pursue avenues to make the commercialization of Patel’s compound a reality.