Michael Laflamme was a PhD student when he first saw a rodent’s heart muscle cells contract under a microscope. He was immediately fascinated how an electrode could control the beat of the cell.
“It was so different from other cells in the body — you could actually see how hard these cells were working,” he says. “It captured my imagination right away, and it still does 30 years later.”
Today, Laflamme is a senior scientist at University Health Network’s McEwen Stem Cell Institute in Toronto, and his work with heart cells has put him at the forefront of modern medicine.
“The heart is perhaps the least regenerative organ in the body,” he says. “A person typically loses over one billion muscle cells within 30 minutes of a heart attack, and that damage has always been irreversible.” Laflamme and his team are developing a technique that replaces damaged heart muscle cells with new ones regenerated from stem cells. The ability to permanently restore heart function will be life-altering for the nearly 600,000 Canadian adults living with heart failure.
Laflamme’s project is funded by University of Toronto’s Medicine by Design program, which receives funding from the Canada First Research Excellence Fund. And it’s an example of how cell and gene therapies (CGTs) have the potential to completely transform health care. Whereas conventional drugs simply manage symptoms, these cutting-edge therapies are engineered to directly attack disease.
Cell therapy begins by reprogramming basic skin or blood cell samples into induced pluripotent stem cells (iPS), which can then be matured to replace any damaged cell in the body. And gene therapy can alter or disable a patient’s faulty disease-causing genes, allowing healthier copies to move in and help them heal. Research on both has progressed with such efficacy that the idea of finding cures for such diseases as Parkinson’s, leukemia, diabetes and heart failure is no longer far-fetched.
“This is the health field of the future,” says Cate Murray, president and CEO of the Stem Cell Network (SCN), an Ottawa-based non-profit that was one of Laflamme’s early funders. According to a recent report by Canada’s Innovation Economy Council, the global market for CGTs is expected to grow to U.S.$34 billion by 2030 — a significant increase from U.S.$4.4 billion in 2020. Such a boom will open up significant opportunity, but Canada’s biotech sector has been slow to get in the game — of the six cell and gene therapies to so far get the green light from Health Canada, none were commercialized in this country.
Murray says the federal government’s recent $1.2-billion budgetary commitment in biomanufacturing and life sciences will be a big step toward developing domestic intellectual property, and keeping it in the country. “The science has been moving at warp speed and as it does, so does our need to industrialize it,” she says.
Leveraging Canadian expertise
Regenerative medicine has its origins in Canada. Stem cells were discovered in the early 1960s by University of Toronto researchers James Till and Ernest McCulloch, while Michael Smith, of University of British Columbia, won the 1993 Nobel Prize in Chemistry for his role in discovering site-directed mutagenesis, an early technique used in genetic engineering.
“In Canada, the focus has always been on great science, but we’ve traditionally been slower to leverage our expertise,” says Michael May, president and CEO of the Centre for Commercialization of Regenerative Medicine (CCRM), another non-profit aiming to foster homegrown cell and gene therapies. “If we’ve learned anything from our struggle to develop COVID vaccines here, it’s that we need to build up our own industry.”
When CCRM was established in 2011, there were only a handful of Canadian companies exploring the potential of cell and gene therapy. None were well-funded. Today, there are almost 60, a dozen of which were incubated at CCRM. One of its biggest successes is Vancouver’s Notch Therapeutics, which is developing a pipeline of cellular immunotherapies. “After more than a decade of research, they were able to raise $110 million in just over two years,” says May. “That’s what we’re looking for. Our goal is to help translate exciting research into clinical trials. And to move from the lab to the clinic and then into the market, we first have to tackle manufacturing.”
Manufacturing cell and gene therapies at commercial scale will be both costly and difficult. “We can’t just throw up four walls someplace in Brampton and call it a manufacturing plant,” says May. “We need a large space with multiple clean rooms, cryo storage and a well-run supply chain.” This summer, OmniaBio, a CCRM contract manufacturing subsidiary, will break ground on a $580-million, 200,000-square-foot facility at Hamilton’s McMaster Innovation Park. By 2032, according to a CCRM study, the facility is expected to generate $4 billion annually to Ontario’s GDP and $450 million a year in tax revenue.
Upfront investment could also have a significant effect on the consumer’s end, where the cost of regenerative medicines can be prohibitive. The average price for most treatments is currently in the six figures. Some, like Novartis’ Zolgensma, a one-time treatment for spinal muscular atrophy, comes with a staggering price tag of $2.8 million. “What will the pharmacy of the future look like?” says May. “And how will health insurance handle reimbursement? We don’t know yet. The one thing we do know is that lower costs can only come with the creation of a complete Canadian CGT ecosystem.”
More than just lower costs, the burgeoning industry will also encourage the next generation of researchers to develop all the soft skills needed to spin out their own companies — from a knowledge of regulatory pathways to the knack for accessing public and private funding.
“I’m used to thinking like a scientist,” says Maryam Faiz, an assistant professor at University of Toronto’s Department of Surgery. With funding and advisory support from Medicine by Design, she’s now working on creating a company focused on a cell regeneration treatment for nervous systems damaged by multiple sclerosis. “Now, I also have to think about intellectual property and about competitors and timelines. It’s a whole different sort of adventure,” she says. “The lesson I’ve learned is it’s OK to think big.”
Laflamme, who expects his cardiac cell therapy to be ready for clinical trials within four years, couldn’t agree more. “Right now, the only option for end-stage cardiac patients is a transplant,” he says. “And there just aren’t enough donor organs available. The ability to regenerate heart muscle cells will save hundreds of thousands of lives. If that happens, I will retire happy.”
The MaRS Impact Health conference, being held May 25 to 27, explores the latest innovations in biotech.
Howard Akler writes about technology for MaRS. Torstar, the parent company of the Toronto Star, has partnered with MaRS to highlight innovation in Canadian companies.
