Undergraduate researchers find potential new therapies to treat severe epilepsy
Drosophila, a tiny fruit fly, may hold the key to identifying new drug therapies to help individuals coping with a particularly devastating type of epilepsy known as Dravet syndrome.
A team of undergraduate researchers from the Biology Program in York University’s Faculty of Science is working with biology sessional lecturer Kyle Belozerov to test different central nervous system (CNS) specific drugs and their effectiveness in alleviating the symptoms of Dravet syndrome. Thus far, the team has tested several dozen of CNS-specific drugs using genetically modified fruit flies and found two candidate compounds that reduce the severity of seizures.
The students, April Kong, Fojan Talaei and Lisa Shim, are using a particular type of Drosophila with a mutation in the fly analog of the human SCN1A gene. In humans, mutations in SCN1A located on chromosome 2 are responsible for an array of seizure disorders ranging from simple febrile seizures to the most severe form of epilepsy known as Dravet syndrome.
“I am genuinely impressed with the enthusiasm and dedication that Fojan, April and Lisa demonstrated working on this important project,” said York University Biology Professor Arthur Hilliker, whose lab is hosting the researchers. “I applaud Dr. Belozerov’s leadership for providing this unique and meaningful research experience to York undergraduates. Thus far, the team has tested more than 50 CNS-specific drugs for their effect in the Dravet syndrome model and found two compounds that alleviate seizures in flies. These drugs were not previously known to be effective in the treatment of epileptic seizures and therefore, these findings may prove extremely beneficial for patients in the future.”
Epileptic seizures devastate the lives of millions of people around the world and represent a formidable healthcare challenge due to the lack of effective therapeutic treatments. Drug therapies have varied effectiveness because seizures are caused by mutations in a large number of different genes and each mutation responds differently to a given therapeutic intervention. Intractable epilepsy syndromes do not respond to any currently available medications. Dravet syndrome is particularly devastating because it causes cognitive and behavioral impairment in very young children. The gene mutated in Dravet syndrome, SCN1A, is expressed in the brain and produces a voltage-gated sodium channel.
“Fruit flies are amazingly useful models of human disease” said Talaei. “Flies with the Dravet syndrome mutation display severe uncontrollable muscle movements reminiscent of the human seizures. It is fascinating that the mutations in this gene cause similar symptoms in both flies and humans, although the two animals are separated by 600 million years of evolution.”
“Because of this remarkable preservation of gene function between flies and humans we can quickly and inexpensively test the effects of a large number of drugs on seizure progression in flies,” said Kong.
“We can then identify a few promising candidates for further research,” added Shim.
In addition to the team’s discovery, the project is significant because it provides students with a valuable experiential learning opportunity. “As a biology educator, I strive to narrow the gap between the textbook concepts that students learn in the classroom and real-life applications of biological research,” said Belozerov. “I utilize the fly model in my own research and find it exciting to be able to show students how this simple laboratory organism can yield information with a potential to improve the lives of millions of patients.
“I believe that offering a variety of research opportunities to interested students as a supplement to their classroom studies is a critical component in delivering a world-class educational experience here at York University,” said Belozerov. “I am proud to have the opportunity to contribute to this mission.”