Research is underway at Western that can help improve antiepileptic drug delivery through optimized dosing.
Existing antiepileptic drugs (AEDs) do not match the peaks and valleys of when an epileptic seizure is most likely to occur, forcing patients to consume AEDs three to four times a day.
Chemical and biochemical engineering professor Kibret Mequanint’s research aims to resolve this issue by developing a single, once-a-day (or potentially once-a-week) capsule that delivers doses to match the time of seizure peaks.
Some 300,000 Canadians suffer from epilepsy, a chronic neurological disorder that affects people of all ages and characterized by frequent seizures, according to the Public Health Agency of Canada.
Mequanint and his team, including Schulich Medicine & Dentistry neurology professor and co-director of Western’s epilepsy program Jorge Burneo, received a 2020 Exploration award valued at $250,000 from the New Frontiers in Research Fund (NFRF) to support their anti-epileptic drug delivery research.
The NFRF-Exploration program supports interdisciplinary research that’s considered high-risk and high-reward, providing researchers with the capacity to explore new possibilities with potentially significant impact.
“Most seizures are not random events, but occur in cycles,” said Mequanint.
In 80 per cent of patients with epilepsy, the 24-hour body clock that regulates a person’s sleep-wake cycle – known as circadian rhythm – affects the timing of seizures. The pattern of seizures varies with the location of the epileptic focus in the brain, Mequanint explained. For example, seizures originating in the temporal lobe occur more often during the day, whereas seizures arising from the frontal and parietal lobe are more frequent during sleep.
“We cannot change a person’s circadian rhythm, so our goal is to harness it for chronotherapy,” said Mequanint. “We adjust the dosage of drugs to match the times of highest seizure occurrence and susceptibility. For instance, with frontal lobe seizure treatment, the capsule would release lower doses during the day and higher doses during the night.”
One issue with oral drugs is that, shortly after being swallowed, the capsule disintegrates and releases its contents, and the body then quickly metabolizes the drug.
“So, how can we keep the capsule in the stomach for a longer time without it disintegrating and metabolizing?” asked Mequanint.
The team’s proposed oral delivery system is packaged in such a way that the small, easy-to-swallow capsule has three layers, absorbs acid from the stomach to expand, and releases the drug through pulsation for a longer period of time rather than a constant amount.
“By reimagining how patients take oral AEDs, we envision a future where seizure times are precisely matched with increased drug dosage for maximum efficacy and without toxic effects,” Mequanint said. “It also greatly increases patient compliance, since confusing dosing schedules, medication mix-up, and cognitive impairment with aging are major issues when ingesting oral tablets three to four times a day.”
Perfecting the right timing and right dosage with the right patient has the potential to revolutionize the treatment of epilepsy.
“We are very excited about the interest and enthusiasm it has already generated among neurologists and reviewers of our proposed AED delivery technology,” said Mequanint. “This work builds on my existing research and Western’s excellent clinical epilepsy program.”