“Functional cure” for type 1 diabetes passes first human trials
A pair of new studies are reporting results from a landmark type 1 diabetes human clinical trial testing the safety and efficacy of an implantable device containing stem cells designed to mature into insulin-secreting cells. The experimental implant was found to be safe, well-tolerated and mildly effective, offering promising signs that with further optimization the treatment could present diabetics with a “functional cure.”
In 2017 researchers kicked off a Phase 1/2 human clinical trial testing an experimental implant designed to replace the missing insulin cells in type 1 diabetics. The device has been described as a “functional cure” for type 1 diabetes. This means it isn’t a direct cure, addressing the autoimmune roots of the disease, but rather it helps the body maintain normal blood sugar levels by compensating for missing insulin-producing cells.
The treatment follows on from prior successes transplanting functional pancreatic islet cells from donors into patients with type 1 diabetes. Instead of relying on donor cells the new device uses human pluripotent stem cells (PSCs) engineered to develop into pancreatic cells.
The stem cells are loaded into a device and implanted into diabetic patients. Those cells then hopefully mature in the body, becoming islet tissue that includes the beta cells that produce insulin when needed.
"The present study demonstrates definitively for the first time to our knowledge, in a small number of human subjects with type 1 diabetes, that PSC-derived pancreatic progenitor cells have the capacity to survive, engraft, differentiate, and mature into human islet-like cells when implanted subcutaneously," says Howard Foyt, from ViaCyte, the company working on the new innovation.
The new studies report on the first 26 patients treated with the device. At the one-year follow-up after implantation the cohort spent an average of 13 percent more time in a healthy blood glucose range and insulin requirements were reduced by an average of 20 percent.
These findings indicate the device works, however, whether it generates clinically meaningful blood glucose improvements is unclear. David Thompson, a researcher working on the trial from the Vancouver General Hospital Diabetes Centre, says the treatment is currently being improved to find ways to deliver higher volumes of PSCs and potentially achieve better results.
“Because of this initial success, we are now implanting larger numbers of cells in additional patients and we hope that this will result in a significant reduction or even elimination of the need for patients to take insulin injections in the near future,” says Thompson.
Another issue that will need to be overcome before the treatment is widely available is the need for the device to be accompanied by constant immunosuppressive medications. Early research found that without suppressing the immune system a human body quickly rejects the implanted device. The only serious adverse effects detected in this preliminary human trial were from the immunosuppressive treatment accompanying the implant.
Commenting on the new studies, diabetes researchers Eelco de Koning and Francoise Carlotti call the new findings a milestone while pointing out a number of questions that will need to be answered as trials progress.
Where is the best site in a body for the device to be implanted? How long do these cells stay viable and produce insulin? Will the treatment need lifelong immunosuppressive drug therapy to be viable and what is the long-term safety profile?
De Koning and Carlotti suggest the treatment may still be several years from general clinical use but these early clinical trial findings indicate promising ways to target type 1 diabetes in the future.
“The clinical road to wide implementation of stem cell-derived islet replacement therapy for T1D is likely to be long and winding,” write de Koning and Carlotti. “Until that time, donor pancreas and islet transplantation will remain important therapeutic options for a small group of patients. But a landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with T1D. An era of clinical application of innovative stem-cell-derived islet replacement therapy for the treatment of diabetes has finally begun.”