Islet cell transplant trial outcome ‘major milestone' toward cure for diabetes

Globe and Mail

20-06-2025

When Amanda Smith learned at the age of 25 that she had late-onset Type 1 diabetes, she considered the diagnosis a death sentence.
The nurse, from London, Ont., had a particularly dim view of the disease because she grew up watching her mother struggle with it. Her mother would slur her words and lose consciousness when her blood sugar bottomed out. Once, Ms. Smith's grandfather had to break a window to reach her mother, who was passed out in her home holding a banana she had tried to consume to raise her blood sugar.
'It literally eats you from the inside out,' said Ms. Smith, now 36. 'It rots your teeth, it destroys your body, your vision. The complications that come with Type 1 diabetes are so extreme.'
Ms. Smith is confident now that those complications won't be in her future. In February of 2023, she became the first Canadian to receive a transplant of islet cells – the cells in the pancreas that make insulin – derived from embryonic stem cells.
The transplant freed her from insulin and gave her blood sugar control akin to a non-diabetic. It was performed at Toronto General Hospital, the institution where insulin was first tested more than 100 years ago.
On Friday, the results of the clinical trial in which Ms. Smith participated were published in the New England Journal of Medicine. The early-phase trial was small, and the procedure has a significant downside in that patients must take anti-rejection drugs for life, just like recipients of organ transplants.
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Nonetheless, the study's outcome counts as 'spectacular,' according to James Shapiro, who holds the Canada Research Chair in transplant surgery and regenerative medicine at the University of Alberta and was not involved in the study. Ten of the 12 participants who received a full dose of the cells were insulin-independent one year later.
'This is a major advance and a major milestone along the journey towards a cure,' he said.
Dr. Shapiro was himself responsible for an earlier breakthrough on that path. In 2000, he and his colleagues at the University of Alberta published a seminal paper on a method they developed for safely and effectively transplanting islet cells from deceased donors into patients with Type 1 diabetes. They dubbed their regimen the 'Edmonton Protocol.'
'We used to call it the drive-through transplant,' Dr. Shapiro said, because giving patients islet cells was less risky and burdensome than a whole pancreas transplant. The cells are infused into patients under mild sedation with an IV-drip into the portal vein of the liver.
The breakthrough described in the new paper is that the islet cells transplanted into Ms. Smith were derived not from deceased donors but from embryonic stem cells, which function as a type of source code that scientists can coax into becoming any cell in the human body.
The supply of such lab-created islets could, in theory, be limitless, unlike the supply of deceased donor islets.
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Trevor Reichman, director of the pancreas and islet transplant program at the University Health Network's Ajmera Transplant Centre, said the most encouraging result is that the islet-cell transplants eliminated dangerous blood sugar 'lows' that can cause confusion, seizures and unconsciousness. He ran the study site at UHN and is an author of the new paper.
'All of them, essentially, were able to get rid of their hypoglycemic episodes,' Dr. Reichman said, 'so all of the real risks to them, all of the lows, were essentially eliminated.'
Still, the international trial, funded by Boston-based Vertex Pharmaceuticals, wasn't without its challenges.
The company paused it temporarily last year after two participants died, though not from taking Zimislecel, the brand name of the new islet therapy. Vertex expects to apply for regulatory approval of Zimislecel starting next year.
One participant died of severe dementia 30 months after the infusion. That patient had pre-existing neurocognitive impairment and, before joining the trial, had suffered a brain injury during a motor-vehicle accident caused by a severe blood sugar low.
The other died of cryptococcal meningitis, a fungal infection caused by a sinus surgery. The death was related to the immunosuppressant medication that the participant was taking to preserve the islet transplant, the study said.
That death underscores the tradeoff that people with Type 1 diabetes would have to make with Zimislecel, said Rémi Rabasa-Lhoret, director of the Metabolic Diseases Research Unit and The Diabetes Clinic at the Montreal Clinical Research Institute.
He wonders how many people with Type 1 would be willing to take anti-rejection drugs for life, especially now that advances such as insulin pumps have made diabetes easier to manage for some patients.
'It's probably going to be a very narrow population,' Dr. Rabasa-Lhoret said.
The next step for scientists is finding a way to genetically engineer or encapsulate islets so the immune system won't view them as hostile invaders.
In the meantime, Ms. Smith said taking three pills, three times a day to suppress her immune system is a breeze compared with the round-the-clock work of keeping her blood sugar in check.
Her 10-year-old daughter, Draya, used to say she wanted to become a doctor to cure diabetes. Now, she talks of being a pilot or engineer.
'I would do this a million times over compared to the maintenance I used to have to do to keep myself alive,' Ms. Smith said.