Dr. Michael Fehlings hopes that neural stem cells can help spinal cord patients regain some lost mobility.Thomas Bollmann
Zahra Chehimi’s life changed forever when she was rear-ended at a red light in 2013. The mother of two, who was 40 years old at the time, suffered severe spinal cord injuries and was left unable to move from the chest down. Confined to a wheelchair, Chehimi has lost her independence and her ability to care for her kids in the way she once did. “She doesn't feel normal anymore,” says her husband, Hussein.
In 2014, the Chehimis heard about groundbreaking stem cell therapy work being conducted by Dr. Michael Fehlings, a neurosurgeon at Toronto Western Hospital and a senior scientist at the Krembil Brain Institute. They were, of course, intrigued. “We wanted the opportunity to do something that might help her,” he says.
At the time, Dr. Fehlings, who also holds the Gerry and Tootsie Halbert Chair in Neural Repair and Regeneration, was involved in a study that used neural stem cells provided by a cell bank in California. Chehimi was one of 12 patients in that trial and underwent surgery at Krembil, performed by Dr. Fehlings. With Chehimi under anesthesia, Dr. Fehlings reopened her injury and injected small amounts of fluid containing millions of neural stem cells into Chehimi’s spinal cord. The trial saw some success, with half the patients seeing some modest improvement in sensory function; Chehimi gained a bit of sensation in her toe. More importantly, though, says Fehlings, it showed that neural stem cells could be safely injected into the spinal cord injury.
Finding stem cell success
Stem cell therapy is an exciting area of research, but it’s still in its infancy. Tests have shown that when neural stem cells – cells that when in the embryonic stage generate the nervous system – are injected into the spinal cord they can help repair the injured tissue, but it will still be a while, if ever, before stem cells fully repair a damaged spinal cord.
Dr. Fehlings, along with colleagues in Zurich, the United States and Canada, are trying to get there, though. They’re working on ways to leverage the neural stem cells’ ability to repair tissue in people with spinal cord injuries, a development that would be a major breakthrough for those with these devastating injuries.
Rather than using stem cells from other people, which is what he injected into Chehimi, Dr. Fehlings is working on what he calls “next gen” therapies, where a patient would be treated with stem cells derived from their own bodies, such as from the skin, or bone marrow. These cells could be transformed into neural stem cells using a complicated process called “direct reprogramming technology,” which has seen success in preclinical trials.
The benefit of using cells from the patient and not a donor, explains Dr. Fehlings, is that the patient doesn’t need to go on immunosuppressant drugs, which can have side effects. It also means the cells are more likely to survive. In reprogramming the cells during preclinical trials, they were able to bias them to form oligodendrocytes, a type of cell that is key to the repair process. They have begun discussions with Health Canada to get permission to do a phase 1 clinical trial on human patients with spinal cord injuries.
A game-changing treatment
Currently, treatment with neural stems cells seems to work best in injuries that are less than six months old, says Dr. Fehlings. In the future, he hopes to genetically engineer neural stem cells to target the cystic cavities and scarring that form around an injury that’s more than six months old, so he can help all spinal cord patients. “There are over a million people in the U.S. and Canada who have chronic spinal cord injury. The implications for these individuals is enormous,” he says. “We're really entering a new era of regenerative medicine.”
Dr. Fehlings’s main target is injuries to the cervical region, which make up two-thirds of spinal cord injuries. He’s already made progress on research that may one day help patients who have developed breathing problems from their cervical injuries. Earlier this year, he and his team employed a novel strategy to target a dormant group of neurons located in the cervical area of the spinal cord. When stimulated, these cells, called interneurons, activated and were able to restore breathing following an injury. "The big takeaway here is the identification of this novel neural circuit," said Dr. Fehlings in a press release. "What we found is if we activate this population of neurons using pharmacogenetics, we can rescue breathing."
Generally, thought, patients with cervical problems “are the most devastated from their injuries,” he says. “They lose the use of their hands and arms, and so they lose their independence.” If these patients can regain the use of their hands and arms, as well as control of their bowel and bladder then that would be a “game changer,” he says. While not the primary focus, Dr. Fehlings would obviously be pleased if patients were able to walk again.
Stuart Howe, CEO at Spinal Cord Injury Ontario, says that while it’s possible to live a full life with a spinal cord injury, “there’s no getting around that it’s one of the most instantaneous and life-changing injuries a person can experience,” he says.
Any new procedures that can bring even a little mobility back to someone who has suffered a spinal cord injury, would be significant. “It’s exciting to imagine new therapies, as even a small amount of increased dexterity or function has the potential to revolutionize a person’s level of independence,” he says.
While Chehimi had hoped the surgery would make her more mobile, she and her husband are still happy that she went through the therapy. “Somebody has to take the risk,” says Hussein. “Even if we don’t benefit, it will help others.”
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