Is Canada ready for human trials on stem cell therapy?

Before his accident, Mike Kowalski loved fast motorcycles. At 26, he rode his bike from his home in Markham, Ont., three hours north to Haliburton—it has “nice roads and less cops,” he says—when he took a turn too fast. Hitting a gravel patch, Kowalski lost control. His first and only motorcycle crash left him paralyzed from the chest down. Devastated, he tried to be optimistic: rapid advances in stem cells seemed to suggest powerful new treatments on the horizon. “I was mentally prepared for five years,” Kowalski says. “Not to be back where I was, but that I’d be using a cane instead of a wheelchair.”

Kowalski kept up with the latest research, attending conferences and chatting with scientists about their work in stem cells. As time went by, and treatments failed to materialize in North America, he got increasingly frustrated. Two years after his accident, he went to Taiwan, where an experimental “nerve cocktail” was injected into his spine. Five years later, he went to Beijing and received an embryonic stem cell transplant. Neither treatment, which cost about $20,000 each, made much of a difference, he says. He kept waiting. “Five years came and went, and then 10.” It’s now been 11 years, and Kowalski still uses a wheelchair. “It seems incomprehensible that we can fix rats in a lab and fly rovers to Mars,” he says, “but we can’t regenerate some nerves in my spine.”

Stem cells, which can grow into any cell type in the body, have been touted as a potential cure for everything from type 1 diabetes to stroke. They aren’t without controversy—embryonic stem cells come from discarded human embryos—but they hold huge promise, too. This is certainly true when it comes to spinal cord injury, a devastating condition that affects about 86,000 Canadians. Unlike muscles, organs, skin and blood, the central nervous system can’t repair itself; despite huge advances in treatment and rehabilitation for this type of injury, the damage is often permanent. In theory, stem cells could be injected into a damaged spinal cord to promote repair. Now one influential Toronto neurosurgeon says it’s time to take stem cells out of the lab and into the clinic.

Dr. Michael Fehlings, medical director of the Krembil Neuroscience Centre at Toronto Western Hospital, makes his case in the October issue of Neurotherapeutics. Cell therapies shouldn’t be “stalled at the animal model stage,” he writes. No rat, pig or monkey can perfectly mimic the human condition; after years of working on these animals in the lab, we should pursue “focused, safe and ethical” trials in humans. All new therapies carry their risks. Stem cells “can make anything, but that’s also the danger,” he told Maclean’s in an interview. If they were to grow out of control, these cells could potentially turn into cancer. One argument for moving forward is to stop patients like Kowalski from making desperate trips overseas. “I’m not in favour of medical tourism,” Fehlings says. If patients receive stem cell treatments, “it should be in a carefully regulated clinical trial, with fully informed consent, and they shouldn’t be charged.” After all, we still don’t know if these treatments will work. “We’re hopeful,” Fehlings says, “but there’s a difference.”

A small number of trials have already begun, Fehlings points out, but they’ve faced “incredible hurdles” in getting approved. Geron, the California company now conducting the first human clinical trial of an embryonic stem cell-based therapy, had to submit a 21,000-page application to the U.S. Food and Drug Administration (FDA) outlining 24 different animal studies before it got the green light. Using stem cells derived from human embryos that were discarded after fertility treatments, Geron’s technique transforms stem cells into crude versions of nerve cells, which are injected into the spinal cord. It showed good results in lab rats, who regained some function. Geron’s phase one clinical trial was launched last year; four patients have received transplants, with no adverse effects from the cells or surgery reported so far.

In Canada, there have been no human stem cell trials, in part because government regulations are quite strict. “If anything, the bars here are even tougher,” Fehlings says. “The science has moved at a rapid pace. It’s a very daunting task for regulators to stay up to speed.” Freda Miller, another star Toronto researcher, believes there’s good reason to be cautious. “A lot of us are nervous about those trials,” says Miller, a senior scientist at the Hospital for Sick Children Research Institute and a University of Toronto professor. Any stray embryonic stem cells left over in the cell preparation could be a danger, she says. “It would be a death knell for stem cell-based therapy if an ill-conceived trial led to a patient having a tumour in the spinal cord.”

Beyond that, scientists debate whether lab rats tell us enough about spinal cord injury to safely attempt these treatments in humans. In his paper, Fehlings calls it an “unrealistic hurdle” to expect researchers to validate all their findings in bigger animals, like pigs and monkeys, before launching a clinical trial. “If every treatment had to be replicated in monkeys, we would never move forward,” he says. But Miller points out that a lab rat isn’t the ideal stand-in for a person with an injured spinal cord. “The size of a lesion in a rat is very different, and their spinal cord is somewhat different,” she says. “Even if you injure them badly, they can get some hind leg locomotion back, which is not the case for humans. You can’t predict what would happen in humans on the basis of a rat.”

Miller is concentrating on Schwann cells, a type of cell not found in the brain or spinal cord that helps peripheral nerves to function and heal. Several years ago, McGill University’s Albert Aguayo showed that transplanting Schwann cells into the central nervous system could help it regenerate; in 2007, Miller found a way to derive stem cells from a patient’s skin and then generate Schwann cells. Today, her lab makes Schwann cells in Toronto, then flies them to Vancouver, where they’re transplanted into lab animals for study. She and her team are “laying the groundwork” for a clinical trial in Canada, she says, which she hopes to begin in the “not-too-distant future.”

Using a patient’s own cells to treat their injury, instead of donor cells, could be ideal. Doctors wouldn’t have to worry about rejection, Miller says, and there would be no ethical conundrum. A team at the Miami Project to Cure Paralysis, based at the University of Miami, is awaiting FDA approval for another trial involving Schwann cells, and hopes to start enrolling patients in late 2012. They’ve developed a way to harvest a patient’s mature cells from a nerve in their leg, grow a lot more of them in the lab, and then transplant them into their injured spinal cord to promote healing. This technique doesn’t require stem cells, although they could theoretically help. “If you could take a skin sample and then make different kinds of cells, that would probably be much more user-friendly,” says Kim Anderson-Erisman, director of education. “There’d be no need for a biopsy.”

Despite the urgency of scientists in the lab, it isn’t clear how many patients with spinal cord injuries would actually opt for stem cell treatments, even if they were available, which is highlighted in a 2011 study co-authored by Judy Illes, a neuroethicist at the University of British Columbia, who interviewed individuals with spinal cord injury about their experiences. People tend to think all patients are fixated on walking, but this study noted that it isn’t necessarily the main goal. Depending on the type of injury, they could view regaining the use of their arms and hands, improved bladder and bowel control, or sexual function as their highest priority. And as the study points out, patients’ views can shift over time. The longer they adapt to living with their injuries, the less likely they seem to be inclined to enrol in a clinical trial, which might uproot them again. One said, “The transition was hard enough the first time; I don’t want to go through it again.”

Of the few existing clinical trials, including Geron’s, most recruit patients “at very acute time points,” a week or two after the injury, Illes notes. “We would never say, ‘Stop the science,’ ” but the goal is to determine the best ways to make sure patients give well-informed consent and “do not make one-time, sudden decisions at a time of tremendous life change and desperation.”

It will realistically be decades before most patients can benefit from stem cell treatments. In the meantime, better surgery, drugs and rehabilitation have dramatically improved outcomes. “In the past, people with severe injuries didn’t tend to live very long,” says Dr. Anthony Burns, medical director of the spinal cord program at the Toronto Rehabilitation Institute, the largest of its kind in Canada. “That’s changed a lot. With diligent and appropriate care, their lifespans are approaching those of able-bodied individuals.”

The benefits were clear on a recent morning in late October at the Toronto Rehab facility, where Gord Sloan, a 54-year-old farm owner from Schomberg, Ont., exercised on a treadmill. Wearing a harness, he took careful steps while physiotherapist Trish Stapleford braced him. Sloan had surgery on Sept. 5 to remove a benign tumour from his spine, and he came to the centre as an in-patient shortly after. At the time, he was “flat on his back,” he says. Sloan has been working closely with Stapleford and on his own, spending hours at a stretch in the gym. That day, as she helped him take halting steps backwards, he said, “it’s a long way from early September.” Sloan’s discharge date is Nov. 11, and he hopes to walk with a cane.

Kowalski has adjusted to living with his injury, too. Just over a year before the motorcycle accident, he got married. “We stayed together,” he says. “Many don’t.” Three years later, they had twins, a boy and a girl. He’s stopped following the latest research as closely as he once did. “It’s painful to live and breathe it like I used to do, and not see it come to fruition,” he says. “I backed off, and focused on my kids and work. You can choose to be miserable, or choose to be happy.” Even so, Kowalski admits he’d seek out another experimental treatment overseas if one became available. “I want my life back,” he says, “or as close to it as possible.”