McGill, industry, CQDM and Brain Canada collaborate for drug discovery

Novel drug could provide hope to those suffering from neuropathic pain and insomnia

A diverse consortium, combining expertise from McGill University, the Quebec government and private industry, has made significant headway in the development of a novel new drug that could alleviate insomnia and neuropathic pain. These advances were made possible thanks to a $658,422 grant from the Quebec government (MEIE) awarded by the Consortium Québécois sur la Découverte du Médicament (CQDM), a $453,125 grant from Brain Canada,  and a combined grant from Quebec-based Delmar Chemicals (now Minakem Montréal) and a public institution (CIHR), amounting to a total of $1.6 million for the research.

The journey began in 2007, with a scientific discovery made at McGill and the Research Institute of the McGill University Health Centre (RI-MUHC). Gabriella Gobbi, MD, PhD, Professor, Department of Psychiatry at McGill University and scientist at the RI-MUHC, was studying compounds that had the potential to alleviate anxiety and depression. “One of these compounds had an unexpected effect on a melatonin receptor in the brain, sending the laboratory animals into a deep sleep,” she recalls.

Melatonin is a hormone that helps regulate circadian rhythms (our night and day cycle). It is released primarily by the pineal gland at dusk in response to reduced light levels, which is why it is sometimes called the ‘hormone of darkness’. Melatonin naturally interacts with two receptors in the brain, known as MT1 and MT2, which are selectively specialized in controlling brain functions.

“By pure serendipity, the compound we tested turned out to be an agonist for MT2,” explains Dr. Gobbi, who is also a researcher at the RI-MUHC. The compound didn’t just induce sleep, it also increased the restorative sleep, which is known as non-rapid eye movement (NREM) sleep – the kind of deep sleep that the body needs to stay healthy.

“Insomnia is a huge issue that can hinder daily functioning and trigger major health concerns, such as depression, diabetes and even cardiovascular disease.”

Dr. Gobbi

According to estimates from the Canadian Institutes of Health Research, nearly 24% of Canadians suffer from a sleep disorder.

Several years after this initial discovery, Dr. Gobbi found that lower doses of the same compound reduced neuropathic pain – a condition for which there are very few treatments. “Most pain medication is dominated by opioids, which have associated problems like addiction,” explains Dr. Gobbi. “The identification of novel analgesics is of keen interest in medicine, and we started to realize that the melatonin MT2 compound we had been testing, might have great potential as a medicine to alleviate pain and insomnia.”

Bringing a new drug to market is no small achievement, however. Dr. Gobbi describes the journey as a daunting Via Crucis.

“Most drugs never make it to the clinical phase. There’s a ‘Death Valley’ in drug development that is notoriously hard to cross and requires significant resources, frequently from venture capitalists, which are primarily profit driven.”

Dr. Gobbi

A recent study in the Journal of the American Medical Association (JAMA) estimated the average cost of the investment needed to bring a new medicine to market at $1.3 billion USD; other estimates place the figure significantly higher.

CQDM, which facilitates collaboration between universities, industry and government to accelerate scientific discovery into vaccines, therapeutics and diagnostics, while generating benefits for the Quebec economy, was able to help identify a solution closer to home.

“We are incredibly lucky to be based here in Quebec and have access to these resources. Thanks to McGill’s leadership and administrative support, and funding from the CQDM, Brain Canada and Delmar Chemicals, we’ve been able to build a consortium that also includes members of the pharmaceutical and biotech industry.”

Dr. Gobbi

The first challenge faced by the consortium was to create a viable prodrug for toxicology testing, as the original compound was insoluble because of its lipophilic properties. Enter Robert Zamboni, PhD, Adjunct Professor of Pharmacology, Biochemistry and Chemistry, whose team engineered a new drug from the parent molecule that could be taken orally and metabolized in the body. “It was a highly complex process that took over a year to complete,” recalls Prof. Zamboni. There are many obstacles that academic research needs to solve for translating an idea into an approved drug to help millions of patients. Delmar Chemicals helped McGill researchers to synthesize the drug in large scale and solve biochemical issues. Industry partners, Delmar Chemicals and Evotec were crucial collaborators in completing the synthesis of the drug and the Pre-IND (Investigational New Drug) toxicology work on this reengineered molecule. The GMP facilities and the R&D center of Delmar Chemicals is still available to support the project in the following steps until the final validation and approvals by Health Authorities.

Dr. Gobbi and the team can now look ahead to the first human trials. “It’s an incredible achievement that would not be possible anywhere else,” she says. “I’m proud to be part of a unique collaboration of organizations that have worked together to harness Quebec intellectual property and develop a drug that has the potential to positively impact the health of millions of people.”