French biopharma company Adocia has established a first proof of concept for its AdoShell Islets implant by achieving glycemic control without insulin injections in immunocompetent diabetic rats during a 132-day study.
AdoShell Islets is an immuno-protective synthetic biomaterial containing islets of Langerhans. After implantation in diabetic animals, the islets encapsulated in AdoShell secrete insulin in response to blood glucose levels. The physical barrier formed by the AdoShell biomaterial allows the implanted cells to be invisible to the host’s immune system while allowing the necessary physiological exchanges to occur for the survival and function of the islets.
The study consisted of implanting islets from allogeneic rats – encapsulated in AdoShell – into immunocompetent diabetic rats. The insulin secreted by the transplanted islets was measured for 132 days and no slowing of secretion was observed during the duration of the study.
At the end of the study the graft was removed, which resulted in an observable drop of insulin secretion and rise in blood sugar levels, the animals rapidly returned to a diabetic state.
At the same time, the animals in the control group (diabetic rats that did not receive AdoShell Islets) were unable to control their blood sugar levels.
Additional ongoing studies in diabetic rats, with the aim of optimizing the AdoShell technology, confirm these initial results, producing insulin and normalizing the glycemia in four diabetic rats for 80 days.
The weight gain of the studied rats – also an important clinical indicator of healthy test subjects – shows that the AdoShell Islets are performing as expected. The rats in the control group are not gaining weight as expected in diabetic rats.
The results will be presented at the upcoming cell therapy session of the PODD 2022 conference in Boston in October.
“This first proof of concept in diabetic rats validates our AdoShell technology. Our purely physico-chemical approach is unique and being not biological it gives us confidence that these remarkable results can be translated from one species to another,” said Olivier Soula, deputy-CEO and director of R&D at Adocia.
More than 40 million people worldwide suffer from type 1 diabetes, also known as insulin-dependent diabetes. In these patients, the beta cells of the islets of Langerhans, cells that secrete insulin, are destroyed by an autoimmune mechanism. As a result, patient survival depends on daily injections of insulin.
Despite the use of insulin, some patients have intensely unstable diabetes characterized by extreme glycemic variability, responsible for iterative and/or severe unfelt hypoglycemia, altering the quality of life and increasing morbidity and mortality.
The prognosis of this so-called ‘brittle’ diabetes is poor, with a mortality rate of between 20 to 50% over 5 years, depending on the study. Brittle diabetes affects about 3 of every 1,000 people with insulin-dependent diabetes.
“Our approach is first and foremost very pragmatic: to use donor cells already used in current therapeutics and to fit into existing protocols. In this way, we hope to make a first treatment available to the most severe patients as soon as possible,” said Gérard Soula, chairman and CEO of Adocia.
In parallel with the development of AdoShell Islets from donor pancreases, Adocia also aims to develop its technology from stem cells, which would ultimately make the technology independent of the number of donors. This could mean it is possible to treat many more patients.
“We are currently working on setting up collaborations with companies that develop stem cells with an ambitious vision: to offer the best curative treatment for diabetes without requiring immunosuppressants,” Gérard Soula said.
“Adocia’s results are remarkable, having successfully performed the first islet transplantation without the use of immunosuppressants in immunocompetent animals. We are delighted to be actively involved in these unprecedented results,” said Karim Bouzakri, director of CEED (European Center for the Study of Diabetes).
Adocia has a portfolio of drug candidates based on three proprietary technology platforms. These are: BioChaperone technology for the development of new generation insulins and products combining insulins with other classes of hormones; AdOral, an oral peptide delivery technology; and AdoShell.
Adocia holds more than 25 patent families.