Amanda Smith celebrates the day, August 1, nearly two years ago, when she stopped taking insulin to manage her type one diabetes, just a few months after getting a dose of experimental stem cells as part of a study.
“I remember, like, being scared and excited, and it’s history now,” she said.
The 36-year-old nurse and mother is part of a small, but what some call “milestone study,” of patients with Type 1 Diabetes using manufactured stem cells, designed to grow in the liver and become the full array of pancreatic islet cells that naturally control blood sugar levels.
In a study published in the New England Journal of Medicine, researchers report that of the 12 patients who received a single dose of the stem cells, it eliminated the need for insulin in 10 for at least a year and stopped episodes of low blood sugar, or hypoglycemia, which can lead to dangerous complications, even death. For Amanda, the treatment has been a blessing.
Diagnosed with late-onset juvenile diabetes when she was 25, she was plagued with sudden bouts of low blood sugar, or hypoglycemia that would leave her faint, despite close monitoring. The risk was a diabetic coma or worse.
“I get emotional because I’m free from those handcuffs ... I don’t have that looming over me every day,” she said from her home in London, Ont.
“I took it as a death sentence,” she said. “I knew, eventually, like the end is always some sort of complication with diabetes,” she said.
“We’ve ... dealt with a lot of patients that have struggled with diabetes. And to be able to see such a transformational change in their life is just amazing,” said Dr. Trevor Reichman, the lead author and the Surgical Director of the Pancreas and Islet Cell Transplant Program at the University Health Network in Toronto.
Reichman says it is the first time that scientists have seen this kind of response with implanted stem cell-derived islets.
Vertex, a Boston-based biotech company that sponsored the study, derived the cells from embryonic tissue and then found a way to grow stem cells in large quantities.
Researchers, working at centers in the U.S. and at least three transplant hospitals in Canada, infused them into the patient’s liver. Over the next four to six months, Reichman said they transformed into the array of hormone-producing cells found in a normal pancreas, and they were monitoring the patients’ blood sugar levels in real time.
“In the liver, they’re sensing a patient’s blood glucose level, and they’re secreting the appropriate hormone,” said Reichman. adding that these biological replacements appear to sense changes in “seconds or milliseconds. Essentially, it’s the same as your native islet cells would function.”
“I think the data is just so very exciting, so very, very powerful,” said Dr. Peter Senior, director of the Alberta Diabetes Institute at the University of Alberta. He was not part of this study.
“The primary objective of the study was just to show that the blood sugars were better and that people were not having severe hypoglycemia. They blew past that. Ten of the 12 people are off insulin,” said Senior.
“It’s never been done before in history” said Dr. Michael Thompson, director of Vancouver General Diabetes Centre. “It’s first time they a have achieved a high enough levels of insulin in patients,” using a stem cell product.
“It’s a big advance” he added.
But there’s a tradeoff. The patients, however, require immune-suppressing drugs for life, so that the immune system doesn’t destroy the cells.
There are risks to these immunosuppressive medications, including a higher risk of some cancers, infections, and high blood pressure. Amanda says it is nothing like her constant terror that she might slip into a sudden diabetic coma.
“Taking a couple of pills three times a day is nothing. I take it with breakfast, lunch, and dinner. It’s easy. No comparison, none,” she said. “And I know it’s a huge relief for my family, especially my husband, that’s for sure.”
The study also reports that two patients in the study died, one likely as a result of complications from that immunosuppression, which Dr. Reichman says underscores the need for patients to be closely monitored at experienced transplant centers. A second patient, according to the study, died of severe dementia.
Off-the-shelf live cell therapy
The idea of using cells implanted in the body to produce insulin, instead of insulin injections, began in Canada 25 years ago. Researchers in Alberta pioneered the Edmonton Protocol. It uses insulin-producing islet cells removed from deceased organ donors that are implanted into those with hard-to-manage Type 1 Diabetes.
Some 2,500 patients have been treated around the world, according to the University of Alberta, which reports 80 per cent were able to stop taking insulin injections for a median time of 95 days.
But the number of procedures is limited because there aren’t enough organ donors to meet the demand, and patients also require long-term immune suppression.
So, there have been some two dozen companies around the world looking at other ways of getting manufactured islet cells to regulate blood sugar as a replacement for insulin. The Vertex cells, originally called VX-880, have been renamed Zimislecel. The Boston-based pharmaceutical company says it is ramping up production.
“These are fresh, brand-new cells – they’re not 60-year-old cells that have already had a life, and we’re repurposing them,” said Senior, who works in Edmonton. It pushes the boundary of therapy forward because there is the potential to create a renewable source of insulin-producing cells instead of waiting for cells from deceased donors,” he added.
“I think we’ve got a treatment for diabetes where we are no longer constrained by organ donors,” said Senior. “We’ve got potentially a limitless source of cells that could be used, and that is a massively huge step forward in terms of a cell therapy becoming a reality.”
The next step is for someone to produce stem cells that don’t require immune suppression, by either genetically engineering the cells or encapsulating them to make them invisible to immune attack. Several pilot studies are underway.
It’s a welcome advance, according to Senior. While insulin therapy has been a lifesaver for many since its discovery in Toronto by Banting and Best in 1921, it’s never been a cure.
“I think people with diabetes deserve some of the transformative treatments we’ve seen in cancer and other diseases but we’ve been stuck essentially doing the same thing for 100 years,” said Senior.
In Canada, there are some 300000 people with Type 1 diabetes. Thirty-two new cases are diagnosed each day.
The number of new cases per year increased by 34 per cent between 2000 and 2022, according to Breakthrough T1D (formerly the Juvenile Diabetes Foundation of Canada).
Unlike Type 2 diabetes, which is linked to environmental, dietary, and genetic factors, the exact cause of Type 1 diabetes is still unknown, but doctors say the immune system mistakenly attacks insulin-producing islet cells in the pancreas, resulting in a gradual decline in the availability of insulin to regulate blood sugar.
Questions remain
The study is being continued to include a total of 50 patients, in Vancouver, Edmonton, Toronto and the U.S., with Dr. Reichman’s team actively recruiting candidates.
There are still many questions. Dr. Reichman admits that no one knows how long these implanted cells will last. Amanda hasn’t required any insulin injections for almost two years, the longest documented period so far. He adds there are no signs that the other nine, who also went off insulin, have gone back on the injections since their stem cell infusion.
Unclear also is whether this therapy will reduce the longer-term and burdensome complications of diabetes, including heart problems, amputations, kidney failure, and vision loss. However, data from patients treated with the Edmonton protocol, using tissue from deceased donors, show signs of reduced complications, a promising sign for the newer therapy, according to Dr. Thompson.
The other concern is that not all patients with severe hypoglycemia may want to make the same choice as Amanda, swapping the diabetes risks for those that come with the anti-rejection medications.
“Taking a couple of pills three times a day is nothing. It’s easy. There’s no comparison, none,” she said.
Another question is that a single treatment therapy for this disease could come with a very high price tag. “We’ll have to wait and see,” said Reichman.
Amanda Smith, meanwhile, tries to enjoy her freedom with her family and her work at a long-term care home, without thinking too far ahead.
“What happens if the cells stop working or something? You know, I just try and live right now, and I feel so blessed.”
She debates the question - does she have diabetes anymore?
“I don’t take any insulin anymore. I don’t take medication for diabetes anymore. So, I feel like a regular person again without diabetes.”
Correction
This article has been updated to fix a spelling error. The Edmonton Protocol involves cells from deceased organ donors, not diseased organ donors.
