“This is an exciting time in research into the regeneration of insulin-producing cells as a therapy for diabetes,” said Adolfo García Ocaña, head of the Department of Molecular and Cellular Endocrinology at Beckman Research Institute/City of Hope Medical Center. Duarte, California) at the 34th National Congress of the Spanish Diabetes Society (SED), which took place in Valencia.
A small molecule, called harmine, which is capable of considerably increase the number of human insulin-producing cells in vivo in mouse models with transplanted human islets. If we take into account that diabetes is characterized by a deficiency in the number of insulin-producing cells, “these findings could be of great importance for the future treatment of diabetes,” according to García Ocaña, whose research group also noted that “this molecule , together with an anti-CD3 antibody (teplizumab, recently approved by the FDA), induces remission of type 1 diabetes in diabetic mice.”
The promises of this line of research have caught the attention of the global scientific community, mainly due to the therapeutic future they represent. As the expert admits, “there is great expectation about our results in relation to harmine and other molecules of this class of DYRK1A intracellular target inhibitors which, together, showed high efficacy in increasing the number of insulin-producing cells.”
Combined with teplizumab, it was able to induce remission in mice.
Results from García Ocaña's research group (many of which were presented over the past two years at the American Diabetes Society and recently submitted for publication in high-impact journals) indicate that three-month treatment with harmine, in combination with GLP1 receptor activators (such as exenatide, semaglutide, etc.), is capable of increasing the number of human beta cells sevenfold in mice transplanted with human islets. “This means that a diabetic person with a limited number of pancreatic beta cells can multiply that number by seven in three months of treatment. This is very significant”, he says.
In fact, they are already very advanced and phase 1 clinical trials near completion, which are being carried out at Mount Sinai Hospital in New York. The objective is to determine the maximum tolerable dose. We are getting closer and closer to the fact that harmine or another inhibitor of the intracellular DYRK1A target is a therapeutic reality for the treatment of diabetes.
“Although caution must always be exercised until a drug is approved for any pathology, these are very exciting times in research into the regeneration of pancreatic beta cells for the treatment of diabetes”, emphasizes García Ocaña, who guarantees that “every time we are closest to that this research can lead to a therapeutic reality for the treatment of diabetes».
artificial pancreas
Regarding the future of technology applied to this disease that looms on the near horizon, Jorge Bondía, head of the CiberDEM group at the Polytechnic University of Valencia, recognizes that “at the moment artificial pancreas systems, although hybrid, are a reality that is changing diabetes management: not only with better control, but also by relieving the burden of decision-making, which means a better quality of life.”
Still, there is significant room for improvement. “The current challenge is how to eliminate or reduce patient intervention to a minimum, that is, how to gain even better quality of life with these systems”, says the specialist, who points out “several promising lines of work, such as the development of Continuous Glucose Monitor Automatic Intake Detection Methods or even the development of “wearables” for this purpose”. Progress is also being made in multi-hormonal systems, administering glucagon or pramlintide together with insulin and even with concomitant treatments (such as iSGLT2). As Bondía concludes, “substantial progress is being made in the development of fully automatic artificial pancreas systems, although this implies an increase in technical complexity given the limitations of subcutaneous insulin.”
