Montreal doctors explain how stem cells may have ‘cured’ Type 1 diabetes

Stem cell therapy has restored insulin production in about 10 patients with Type 1 diabetes, according to a study published in the prestigious New England Journal of Medicine.

This study, while far from perfect, still brings us a step closer to the day when these patients will no longer need insulin doses to control their blood sugar, commented Dr. Rémi Rabasa-Lhoret, an expert on the disease at the Montreal Clinical Research Institute who came close to participating in this work.

“This is a big step in the right direction,” he said.

Fourteen patients were recruited for this study. Two died during the study, one from cryptococcal meningitis and the other from pre-existing dementia. The need for exogenous insulin was reduced or eliminated in the remaining 12 subjects, to the point where 83 per cent of them no longer required insulin 12 months after the start of treatment.

“Although eliminating the need for exogenous insulin is desirable, the results of this study demonstrate the clinical benefits of restoring pancreatic islet function, even in the absence of complete elimination of insulin treatment,” the authors write.

Restoring pancreatic islet function refers to efforts aimed at either replacing or restoring insulin-producing cells (beta cells) within the pancreatic islets of Langerhans, which Dr. Rabasa-Lhoret says are often damaged or dysfunctional in diabetes.

‘It’s nearly a cure’

Despite not participating in this work, Dr. Rabasa-Lhoret and an expert on the disease, Dr. Yasaman Aghazadeh of the Montreal Clinical Research Institute, say this breakthrough has been shared across the medical community.

“This is really groundbreaking. Years of years of research has been dedicated into this,” said Dr. Aghazadeh. “[It’s] not only important for the future of type 1 diabetes, but also for just regenerative medicine as a field.”

There was also a complete absence of serious hypoglycemic events in the 12 participants who received a full dose of the therapy and completed at least 12 months of follow-up. With this milestone, Dr. Aghazadeh still waves caution when using the term cured, though assures this is a great leap into this direction.

There remains hope, said Dr. Rabasa-Lhoret, “of successfully curing Type 1 diabetes by allowing people to regain the cells that produce insulin.” Currently, this option is only available to a tiny number of patients each year and involves a transplant of either the entire pancreas or insulin-producing cells, which, of course, requires the recent death of a suitable donor.

“Ten without insulin, it’s nearly a cure,” he said.

The patient will then have to undergo an immunosuppression regimen to prevent their immune system from rejecting the transplant, which doctors say is something the field is hoping to shift away from.

The new study faces the same obstacle, since the stem cells used came from foreign donors and not from the patient themselves. In this regard, most of the side effects observed were mild or moderate, the study authors assure, and were primarily attributable to the required immunosuppressive therapy.

“The main drawback (of stem cell therapy) is that you still have to take anti-rejection medication,” said Dr. Rabasa-Lhoret. “And for Type 1 diabetes, we have other options.”

It should be kept in mind, he reiterated, that immunosuppression treatment is anything but trivial, as it carries a significant risk of certain infections and even certain cancers. Thus, even though it is not mentioned in the study, it cannot be ruled out that the cryptococcal meningitis that killed one of the participants was associated with this immunosuppression, added Dr. Rabasa-Lhoret.

“The caveat is that not every single person can receive this because for your body not to reject these cells, you have to actually go under immune suppression regimen, and immune suppression by itself is a very complicated therapy. It can cause significant health issues,” Dr. Aghazadeh explained.

A possible treatment without immunosuppression will involve transforming stem cells taken from the patient into cells capable of producing insulin.

This is easier said than done, however, warned Dr. Rabasa-Lhoret, and the feat has so far only been achieved in a single patient, in a study whose results have not yet been published.

When we take a patient’s stem cells and transform them back into insulin-producing cells, he explained, “we can introduce small differences that could cause the body to start not recognizing them,” which would trigger an unwanted and potentially dangerous immune response.

We must also ensure that these stem cells don’t cause other problems in the medium or long term, for example by transforming into cancer cells, he said.

For Dr. Aghazadeh, she explained that many labs in the U.S., Europe, and Canada are working on modifying these cells in a way that they’re more therapeutic.

‘We’re trying to understand human development’

“We’re trying to understand how these cells are formed in a natural human body and we have realized that just generating them in a dish might not be ideal that they need an environment, a particular environment that is present in the body and we’re actually simply trying to recapitulate this environment in the lab,” Dr. Aghazadeh explained.

“[So] this is quite a complicated and complex system to model but we’re making significant progress on that and the goal is that once we can recreate their environment in the lab, cells that were generated are actually better quality.”

While discussing the program and the medical advancements, Dr. Aghazadeh noted that individuals who are younger than 18 years old cannot be immunosuppressed because this immunosuppression interferes with abnormal development. She adds that this population are the ones most affected by type 1.

“The Holy Grail that patients are looking for is a cure,” Dr. Rabasa-Lhoret reminded us.

But with the solutions currently available for managing Type 1 diabetes, he continued, the drawbacks of immunosuppression become “much less attractive.”

There will inevitably be people who won’t be able to take their insulin or who will have other problems, Dr. Rabasa-Lhoret said “and there will be a small market among these people, but the next step is really the absence of immunosuppression.”

“We now know it’s feasible,” he concluded. “It’s not in mice, it’s not in rats, it’s not in pigs, it’s in humans. We know it’s feasible to transplant cells and produce insulin in patients, which is pretty magical.”

The treatment being tested in this phase 1/2 study was developed by the biotechnology company Vertex, which already made headlines after bringing to market a treatment—also based on stem cells—for cystic fibrosis, which, for the first time, addressed the underlying causes of the disease and not just its symptoms.

–With files from La Presse Canadienne