MRFF grant to fund research into novel epilepsy drugs
Researchers led by the Department of Neuroscience’s Professor Patrick Kwan CIA have been funded $3.8 million in the current round of Medical Research Future Fund (MRFF) grants to develop a new class of drug compounds to counter drug-resistant epilepsy (DRE).
The research, which will span five years, is being conducted in collaboration with Chief Investigators (CIs) from the Monash Institute of Pharmaceutical Sciences (MIPS), Murdoch Children’s Research Institute and Swinburne University of Technology.
It will screen a new class of compounds using cultured neurons derived from human induced pluripotent stem cells, followed by testing in an animal model of DRE, aiming to identify one or two compounds ready for clinical trialling in DRE patients once the project is completed.
Professor Kwan said there was an urgent need to discover new drugs for epilepsy, which affects 70 million people worldwide.
“Our research has shown that despite the development of more than 15 new drugs in the past three decades, the overall treatment prognosis of epilepsy has not improved. This is likely because these drugs act in similar fashions to their older counterparts. Therefore, new classes of medications with radically different mechanisms of actions are needed,” Professor Kwan said.
People with epilepsy have recurrent seizures that cause injury or even death, and have increased physical, psychiatric and cognitive comorbidities. Despite trials of multiple drugs 30% of patients continue to have seizures and are considered to have DRE.
Titled ‘Pre-clinical evaluation of selective adenosine A1 receptor positive allosteric modulators for the treatment of drug-resistant epilepsy’, the project will fast-track the development of the new class of drugs.
CI Dr Ben Rollo said, “By using patient-derived stem cells as the initial screening platform, we will be able to test hundreds of novel compounds without any risk to patients and reduce the reliance on animal testing.”
“We are developing a class of compounds, called ‘positive allosteric modulators’ (PAM). These compounds can enhance the effect of a naturally occurring anti-seizure molecule (adenosine) in our brain, thus harnessing our brain’s intrinsic defence mechanism against seizures,” said CI Dr Lauren May from MIPS.
“By binding to a different region on the target protein, these compounds have the potential to provide selective modulation of seizure activity, and therefore are expected to have fewer side effects,” she said.
“We are extremely excited about the grant because there is a real prospect of introducing a completely new class of drugs for epilepsy treatment. This will lead to direct impact in clinical care and patient outcomes,” Dr Rollo said.
“This research is highly important because new types of medications are desperately needed for patients with DRE,” he said. “As a society we cannot afford to continue ‘business as usual’ in how we manage this devastating condition. Further, if this stem-cell based approach in drug development is successful, it will pave the way for discovering new drugs for other brain diseases.”
The Commonwealth Government’s MRFF has invested more than $30 million in funding for Monash research projects this round, including three Central Clinical School projects.