Co-implantation of allogeneic islets and streptavidin-presenting microgels sustained long-term survival of pancreatic islet cells and provided excellent glycaemic control.

The early-stage regenerative medicine company iTolerance, which is developing technology to enable tissue, organoid or cell therapy without the need for life-long immunosuppression, has announced the publication of positive preclinical results from a non-human primate (NHP) study evaluating co-implantation of allogeneic islets and SA-FasL-presenting microgels for the treatment of diabetes.

The manuscript, FasL-microgels induce immune acceptance of islet allografts in nonhuman primates, was published in the peer-reviewed journal, Science Advances.

Longevity.Technology: There are over 9 million people living with type 1 diabetes, the majority of them living in high-income countries [1]. Neither its cause nor the means to prevent it are known, and although many people with type 1 diabetes now live into their 50s and beyond, it still shortens lifespan and affects healthspan, with men losing about 11 years of lifespan and women 13 [2]. Type 1 diabetes can put you at higher risk of blood clots, as well as high blood pressure, cholesterol and other cardiovascular issues, as well as contributing to retinopathy, kidney disease and nerve damage.

“The NHP data and its publication is a landmark milestone for iTolerance,” said Anthony Japour, MD, CEO of iTolerance. “Chronic immunosuppression carries significant long-term morbidity and mortality risks, including potential for cancer, decline in kidney function, and beta cell toxicity. Eliminating chronic immunosuppression could obviate the need for chronic prophylactic antiviral, antifungal, and antimicrobial agents prescribed to prevent serious infections with immunosuppression regimens.

“Therefore, demonstrating sustained long-term survival of pancreatic islet cells and glycemic control in non-human primates with diabetes without chronic immunosuppression is potentially game changing in the advancement of a possible cure for Type 1 Diabetes.”

Dr Japour added: “Now more than ever, we are dedicated to translating these findings to the clinic and are in ongoing discussions with the US FDA to progress toward human clinical trials [3].”

The NHP study investigated the immunomodulatory potential of the SA-FasL microgel technology in a pre-clinical streptozotocin (STZ)-induced diabetes NHP model in which allogeneic islets and SA-FasL microgels are co-implanted into the omentum, an area of fatty tissue attached to the stomach. Results demonstrated robust glycemic control, sustained C-peptide levels, and graft survival in non-human primates with diabetes for >6 months [4].

Dr García, the company’s Scientific Co-Founder and Executive Director, said: “We are incredibly pleased with the results from this study. Achieving long-term survival of allogeneic grafts without chronic immunosuppression was, until now, an elusive goal. In this very stringent model of islet implantation, we were able to successfully demonstrate a reliable and safe tolerogenic regimen for diabetes without the use of chronic immunosuppression – an exciting finding. We believe this major advancement enables us to take a step toward developing a potential cure for Type 1 Diabetes [3].”

“The use of long-term immunosuppression medications remains the major hurdle for the use of cell and regenerative therapies,” added Camillo Ricordi, MD, Chief Scientist of iTolerance. “The data generated through this NHP study establishes that the approach we have developed may eliminate the need for chronic immunosuppression, a revolutionary approach that I believe will change the way that the scientific research community approaches regenerative medicine [3].”

Dr Ricordi added: “Most importantly, this biomaterial-based strategy offers off-the-shelf immunomodulatory capability without modification of donor islets, increasing its clinical relevance and breadth of potential clinical applicability. These findings are a major achievement that justifies the moving this technology forward towards clinical application in the most expedient and efficient way possible [3].”

[1] https://www.who.int/health-topics/diabetes
[2] https://www.webmd.com/diabetes/news/20150106/type-1-diabetes-linked-to-lower-life-expectancy-in-study
[3] https://itolerance.com/long-term-success-of-allogeneic-islet-implantation
[4] https://www.science.org/doi/full/10.1126/sciadv.abm9881