by Sarah Kasleder for SHRF
In the world of scientific discovery, Dr. Robert Laprairie’s team stands as a symbol of persistence and innovation. Robert's journey has been nothing short of remarkable, from his early days exploring canola pesticide research to his current investigations of the complexities of the endocannabinoid system and trying to find treatments for epilepsy utilizing cannabis.
Seeds of Curiosity Blossom
Dr. Robert Laprairie and Ayat Zagzoog
Photographer: Sarah Kasleder
Robert’s journey in research began unexpectedly. Initially thinking of becoming a high school teacher, he was drawn to canola pesticide research. "One of the things that got me hooked into research was the amazing work and the people I was working with," recalls Robert, reflecting on his early days.
It was the perfect place for his intellectual curiosity to grow.
Guided by a fascination with the brain and neuroscience, Robert pursued further studies under the guidance of Dr. Eileen Denovan-Wright from Dalhousie University in Halifax; he explored the endocannabinoid system and its role in neurological conditions, particularly in Huntington's disease.
Robert reflects upon the research with Dr. Eileen Denovan-Wright, “What Eileen saw is that for people who have Huntington's disease, one of the first things that happens is their endocannabinoid system goes completely dysregulated.”
“The endocannabinoid system is the system of neurotransmitters that we all have in our bodies all the time. They respond to our body's own cannabinoids. These are neurotransmitters like dopamine, serotonin, and adrenaline – the ones people are more familiar with.” Explains Robert, “What that meant is before we develop therapies for Huntington's disease, we need to understand the basics, to the textbook definition, how the endocannabinoid system works.”
Recognizing the importance of the endocannabinoid system in neurological conditions and the significance of how unknown the endocannabinoid system is, Robert's research shifted.
The development of research for the endocannabinoid system was intriguing, especially given the concurrent discussions in Canada about legalizing cannabis, which led Robert to explore other locations for research opportunities.
Homecoming and Collaborations: A Pivotal Location for Groundbreaking Research
The winds of change led Robert back to his roots in Saskatchewan, where he set his sights on exploring cannabinoid compounds and their therapeutic benefits while minimizing harm.
What was fascinating was the great research already performed at the University of Saskatchewan around epilepsy, especially in the last ten years utilizing cannabidiol to treat epilepsy. He started working with various epilepsy researchers who were asking: Can epilepsy be treated with cannabis? "Returning to Saskatchewan was not just a homecoming but a strategic move that brought together diverse expertise. The collaborative spirit here, especially in the realm of epilepsy research, laid the foundation for groundbreaking discoveries. Saskatchewan became the crucible where scientific insights from various disciplines fused, setting the stage for the impactful strides we continue to make."
Ayat Zagzoog and Dr. Robert Laprairie
Photographer: Sarah Kasleder
"The Endocannabinoid system helps regulate or slow down neuro processes. In epilepsy, it is important because, in epileptics, their neurons are overstimulated and overactivated," explains Robert. "If you can use or take advantage of the endocannabinoids to slow the neurons down even further when they are acting inappropriately, maybe you can bring down the severity."
It marked the commencement of his collaborative journey, which weaves diverse perspectives from clinical, preclinical, and chemistry domains. On the clinical front, Dr. Richard Huntsman, at that time a pediatric neurologist at the University of Saskatchewan, specializes in treating children with the most medically complex forms of epilepsy. Complementing this expertise on the preclinical side is Dr. John Howland at the University of Saskatchewan, who is armed with a profound understanding of animal behaviour.
Additionally, Dr. Ganesh Thakur, a chemist from Northeastern University in Boston, played a pivotal role in Robert’s research as his team created the chemicals essential to the project. Notably, Robert and Dr. Thakur share a longstanding collaboration, dating back to Robert’s days as a graduate student.
Promising Compounds and Hurdles
The SHRF-funded project in 2018-2019 for a total sum of $120,000, Modulation of the endocannabinoid system in the GAERS rat model of absence epilepsy, spearheaded by Dr. Robert Laprairie, identified two compounds, GAT591 and GAT593, that reduced seizure severity by 50% in animal models without the “high” normally associated with cannabis.
What makes these compounds particularly promising for treating pediatric epilepsy? Robert explains, "The existing drugs that kids utilize for absence epilepsy, or a lot of other epileptic seizures, only work in a third of kids. That means that two-thirds of kids are not receiving any benefits. In addition to that, a lot of these drugs can have serious side effects such as liver damage if taken for a long period."
Robert further emphasizes, "To the best of our knowledge, we do not have the same side effect profile with our drugs in animal models. We also see a consistent reduction in seizure severity, so we don’t have, for example, only a third responding. All the rats are responding. So, it does give us some hope that we are on the right track."
While this discovery marks a significant win, challenges persist—these compounds have a short duration of action and poor solubility. Robert and his dedicated team are back at the drawing board, refining their breakthrough for greater efficacy and practical application. Discussing the project, Robert shares, "The big win - we found two key compounds that seem to reduce seizure severity by 50%, and the animals were not intoxicated."
The SHRF Impact Award and Beyond
In the realm of research recognition, the SHRF Impact Award holds a special place. This acknowledgement is given to researchers who, having received a SHRF Establishment Grant five years prior, actively contribute to Saskatchewan's research landscape driven by a thorough evaluation process and consider key criteria.
Robert extends a heartfelt thank you to SHRF; “The invaluable support from SHRF acted as a catalyst to the program that would have otherwise been unattainable. Delving into the complexities of studying synthetic cannabinoid compounds in animal models of epilepsy is quite intricate and expensive. The funding was pivotal in kick-starting our research, ensuring seamless operations, providing crucial support to my team, and lifting their projects off the ground. SHRF's backing positioned us as a credible and established research program, which led to getting additional funding from CIHR.”
As Robert reflects on receiving the SHRF Impact Award, it becomes evident that this honour goes beyond merely acknowledging past achievements. The award is a testament to his commitment to building capacity, advancing knowledge, and providing tangible impacts on health, economics, and society.
His commitment extends beyond the laboratory, evident in his active involvement in knowledge mobilization activities. Serving as the Director of Education for the Canadian Consortium for the Investigators of Cannabinoids (CCIC), Robert collaborates with Brain Canada to provide scholarships and a medical education program for physicians. This initiative aims to demystify cannabis and the endocannabinoid system, fostering understanding and awareness in the medical community and beyond. He also works with CRIS, Cannabinoid Research Initiative of Saskatchewan, to provide education about cannabis use during or around pregnancy, showcasing Robert’s dedication to promoting responsible and informed practices in various healthcare aspects.
The Impact Award is not just an acknowledgment; it signifies a commitment to ongoing positive impact, an endeavour Robert passionately upholds.
The experience of winning awards humbles Robert. “I am honoured to win the awards and to give a talk, which is great, but one thing is - I am privileged to lead a team of people. All the work that is going on in the lab is my grad students, – postdocs, and undergrads. I owe much of this to their hard work and am very proud of them.”
Looking to the Future and Cultivating Hope
Robert hopes to extend the scope of his research by testing these compounds in other types of epilepsies. Collaborations with the Universities of Calgary and Sydney, (Australia) will explore Dravet, Lennox-Gastaut, and infant febrile seizures.
Robert’s ongoing research aims to improve the duration and solubility that these compounds can have.
As Dr. Laprairie reflects on his journey, he gives valuable advice to aspiring researchers: "Don’t get discouraged. There is always something to learn in every setback, always something to build from. It will be okay."
Dr. Robert Laprairie's story is about curiosity, collaboration, and a relentless pursuit of knowledge. In the vast landscape of scientific exploration, his work in cannabinoid research not only holds promise for epilepsy treatment but also exemplifies the transformative impact of interdisciplinary collaboration and dedication to advancing knowledge for the greater good.