The University of Tennessee Health Science Center’s Lawrence T. Reiter, PhD, has received a new grant award totaling $418,000 from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. The purpose of this study is to identify currently approved medications that can potentially be repurposed for antiepileptics in both 15q Duplication syndrome (Dup15q) and inherited epilepsy. The outcome of this research could have broad therapeutic impact not only for pediatric disorders like 15q Duplication syndrome, but also for other inherited forms of epilepsy, which result from mutations in synaptic genes.
On average, one in 5,000 people is affected by 15q Duplication syndrome. Children who suffer from Dup15q experience excessively high rates of seizures that often begin after birth as infantile spasms, and later in childhood progress to epilepsy. Symptoms are hard to manage with currently available antiepileptic medications.
“One of the major problems that kids with this duplication experience are difficult-to-control seizures and epilepsy.” Dr. Reiter said. “Our goal is to quickly identify FDA-approved compounds that potentially suppress seizures, and get them to these children faster and in a much more cost-effective manner.”
In this new study, Dr. Reiter will use fruit flies, or Drosophila melanogaster, to replicate the seizures observed in humans with Dup15q. He will perform high-throughput screening to identify compounds that can suppress seizure phenotypes and potentially reactivate gene expression for a specific set of synapse-associated genes that have lower expression in the Dup15q model, some of which are also associated with inherited human epilepsies. His lab will also investigate the molecular consequences of this chemical suppression of seizures.
“Working in collaboration with Dr. Glen Palmer in the UTHSC College of Pharmacy, we developed a plan to screen these flies for drug compounds to potentially suppress seizures,” Dr. Reiter said. “The advantage of using both FDA-approved compounds and natural product libraries is that we can perform clinical trials much faster, since they have already gone through the approval process. Meaning we can go from testing flies to helping treat children with these compounds in a shortened time frame.”
Dr. Reiter is an associate professor in the Departments of Neurology, Pediatrics, and Anatomy and Neurobiology in the UTHSC College of Medicine. His project, titled “An in vivo chemical screen for seizure suppression in Duplication 15q syndrome,” will receive funding for two years.
He is also the recent recipient of a $75,600 funding extension provided by the Foundation for Prader-Willi Research for his project entitled “Gene Expression Analysis in PWS Subject Derived Dental Pulp Stem Cell Neurons,” which uses stem cells from baby teeth to make neurons that represent PWS. He will perform molecular studies on these PWS neurons versus control neurons to identify gene expression changes that are unique to the disease, in an effort to identify new therapeutic approachs to PWS in the near future.