Charting a safer course: Advancements in chronic pain treatment

Chronic pain affects one in every five individuals, yet effective treatment options are far and few between. Too often, chronic pain patients are left to choose between opioids, anticonvulsants for nerve pain and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, all of which present their own negative side effects.

Canadian opioid prescriptions have risen dramatically in recent years, surpassing 20 million prescriptions written annually. Historically known for addiction risks and severe consequences like abuse and overdose, opioids are overprescribed, harmful, and often insufficient to treat pain.

Meanwhile, the over-the-counter accessibility of NSAIDs complicates efforts to mitigate potential interactions with other medications, adding to their adverse effects on the gastrointestinal and cardiovascular systems. Anticonvulsants like gabapentin, used for nerve damage pain, also come with many side effects, like swelling, rashes, seizures, and drowsiness.

Moving pain research forward

“This is the limited arsenal we have right now, and it is simply not good enough. Clinicians and patients are not satisfied with this,” says McGill neuroscience professor and pain specialist Philippe Séguéla, PhD. The Séguéla Lab, , located at the Neuro (Montreal Neurological Institute-Hospital), has studied pain receptors for nearly three decades in the hopes of finding a safer, opiate-sparing alternative to relieve pain. His team has focused on deepening their understanding of the neurobiology of pain, investigating genes, cells and circuits related to pain perception and analgesia – the inability to feel pain.

They were able to identify a class of neuronal receptors – acid-sensing ion channels (ASICs) – as promising targets for pain relief. Their findings suggested that blocking peripheral ASICs could serve as an effective alternative to addictive opioid-based drugs for pain management.

With prior collaborations in the pharmaceutical and biotechnology sectors, Séguéla was driven to leverage his expertise to help chronic pain patients. He admits he was eager to explore the translational and therapeutic potential of these findings rather than solely conducting basic research on ASICs.

“Everyone knows someone affected by chronic pain and feels helpless,” he says. “We need a real qualitative step in the way we approach pain treatment and analgesia. We shouldn’t be afraid of failing, because regardless of the outcome, basic and translational science will have progressed.”

Toward opiate-free treatment of acute and chronic pain

With support from NeuroSphere, Séguéla secured early-stage funding from adMare Bioinnovations and AmorChem in 2020 for the preclinical development of this new therapy and the creation of Neurasic Therapeutics, a biotech company.

“NeuroSphere was pivotal to the creation of Neurasic Therapeutics. The NeuroSphere team was enthusiastic and pushed us forward,” recalls Séguéla. “They came to all our pitch meetings and provided us with support and professional advice. They were very helpful in fine-tuning the message.”

In 2022, Neurasic Therapeutics obtained even more funding from HBHL, CQDM and the Louise and Alan Edwards Foundation through NeuroSphere’s Neuro-Partnerships Program. With three patents filed and past progression to drug safety testing stages, Neurasic Therapeutics is inching closer to phase one clinical trials. If successful, these ASIC blockers could offer an opioid-free solution to the treatment of acute and chronic pain, potentially revolutionizing the field of pain management.

Small part of a larger story

For now, the outlook is highly promising. “In terms of potency and efficacy in vivo, the drug is already a success. Even ahead of testing in humans, we were able to confirm the absence of gastrointestinal side effects,” explains Séguéla. “This potentially offers an interesting clinical avenue, as our drug could be used alongside NSAIDs, reducing the incidence and severity of their side effects.”

In hindsight, Séguéla paints a favourable image of his experience in the corporate side of pharmacology, which can have a positive impact on any lab in the Canadian landscape thanks to its goal-oriented approach. “I like the milestones, the concrete objectives, the precise timeline involved in biotech,” he says. “There may be less freedom and more pressure than in academia, but it is very motivating and stimulating to try to reach tangible goals for the benefit of patients.”

Encouraging researchers to take risks, Séguéla emphasizes the transformative potential of their work: “Commercialization is a very positive experience for the scientists who are willing to dive. We have nothing to lose,” he says. “Even if the venture doesn’t culminate into successful drug development, the optimization of these molecules’ selectivity and potency will at the very least generate unique scientific tools.”

Beyond the potential of his own discovery, Séguéla is optimistic for the emerging treatment options for chronic pain. “Our adventure here is only one small part of a much larger story,” he reveals. “There are currently very interesting clinical trials happening globally, also in the process of testing novel pain targets. There are very promising advancements in the field, all driven by recent progress in the biology of pain. There is hope for chronic pain patients, now more than ever.”