“Functional cure” for type 1 diabetes passes first human trials

“Functional cure” for type 1 diabetes passes first human trials
As well as the primary device (bottom) the trial is implanting patients with smaller "sentinel" implants that will be removed after periods of time so stem cell growth can be measured
As well as the primary device (bottom) the trial is implanting patients with smaller "sentinel" implants that will be removed after periods of time so stem cell growth can be measured
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As well as the primary device (bottom) the trial is implanting patients with smaller "sentinel" implants that will be removed after periods of time so stem cell growth can be measured
As well as the primary device (bottom) the trial is implanting patients with smaller "sentinel" implants that will be removed after periods of time so stem cell growth can be measured

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.”

The new findings have been published in the journal Cell Stem Cell and Cell Reports Medicine.

Sources: University of British Columbia, Cell Press

Promising, but sounds like it's a long way away from making a difference to diabetics. The implant would have to be enormous to deliver enough insulin to displace injection/infusion (and remember Type 1 is typically juvenile onset) and the immunosuppression is a nonstarter. Maybe if they use cells from the patient (although that would be even more expensive to produce)?
Rick O
Sorry, but if this requires immune suppressive drugs, then there's no way I'm signing my son up for something like this. As nerve racking as daily care is, I'm not about to destroy his immune system as an alternative. With Dexcom and Omnipod, and a lot of constant attention, his A1C is continually improving. I'll take that over some other random virus or infection putting his life at risk.
Nice write up Rich.
We have discussed this for years - the only cure for Type I diabetes is to turn off the auto-immune or over-reactive immune system that has attacked and destroyed the beta cells of the pancreas. Any hope of implanting anything that shows traces of similarity to native beta cells will be destroyed as soon as the immune system is triggered. Just like relying on insulin injections - this is not a cure, but a functional work around. With how expensive insulin is (unnecessarily expensive in my book!) this may help reduce patient costs in the USA, but it likely won't reduce the need for regular insulin injections.
A "functional" cure was the discovery of purified animal insulin in standardized concentrations. This is not much better - an invasive procedure that doesn't eliminate the need to test blood sugar and administer additional insulin - is a great "Proof of Concept" but it is hardly any better than the original "Functional Cure" for type I diabetes.
Ursla Valle
I was recently diagnosed with inflammatory arthritis which will require me to take immune suppressant medication to treat. Ive had Type 1 diabetes for 27 years and Hassimotos now for 11 years. I would love to get in on this study!
Stan Mitchell
sernova is doing the same thing,withoutimmune suppression
Central BioHub
Type 1 diabetes, commonly known as insulin-dependent diabetes mellitus (IDDM), is a type of diabetes that affects sugar metabolism. It is caused by the development of autoantibodies such as islet cell antibodies and insulin antibodies against beta-cell antigens by macrophages and T-lymphocytes. It usually starts in children and young people. As a result, it is also called as juvenile diabetes. Furthermore, the incidence of type 1 diabetes has increased in the last decade, affecting the young generation's quality of life.