As the number of people with diabetes worldwide exceeds 500 million, scientists must find ways to improve a limited number of available drugs with unclear efficacy. A new study from Monash University is an important step forward in the development of new therapies.
Scientists have discovered a pathway for insulin regeneration in pancreatic stem cells. They successfully reactivated pancreatic stem cells from a type 1 diabetic donor to express insulin and functionally resemble beta-like cells using a drug approved by the US Food and Drug Administration.
Although more research is needed, the new strategy could, in principle, replace destroyed insulin-producing cells (beta cells) in people with type 1 diabetes with new insulin-producing cells.
Diabetes expert Professor Sam Ei-Osta said: “We consider our research to be novel and an important step towards the development of new therapies. It may lead to a possible treatment option for insulin-dependent diabetes, diagnosed in seven Australian children every day, resulting in lifelong blood glucose testing and daily insulin injections to replace insulin no longer produced by a damaged pancreas.
For the restoration of insulin expression in the damaged pancreas, scientists had to overcome several challenges, as the diabetic pancreas was often thought to be too damaged to heal.
Professor El-Osta said: “By the time an individual is diagnosed with type 1 diabetes (T1D), many of their pancreatic beta cells, which produce insulin, have been destroyed. These studies show that the diabetic pancreas is not unable to express insulin” and that proof-of-concept experiments “address unmet medical needs in T1D. Advances in the genetics of diabetes have brought “greater understanding and a resurgence of interest in the development of potential therapies.”
“Patients rely on daily injections of insulin to replace what the pancreas would have produced. Currently, the only other effective therapy requires pancreatic islet transplantation. Although this has improved health outcomes for people with diabetes, transplantation depends on organ donors, so it has limited widespread use.”
Study co-author Dr. Al-Hasani says that “as we face a globally aging population and the challenges of the increasing number of type 2 diabetes, which is strongly correlated with the increase in ‘obesity, the need for a cure for diabetes is increasingly urgent.’
“Before reaching the patients, many problems must be solved. More work is needed to define the properties of these cells and establish protocols for isolating and expanding them. I think therapy is a long way off. However, this represents an important step towards designing a durable treatment that can be applied to all types of diabetes.”
Professor El-Osta, Drs Al-Hasani and Khurana have developed a revolutionary method to regenerate insulin cells without the ethical concerns usually associated with embryonic stem cells.
Journal reference:
- Al-Hasani, K., Khurana, I., Mariana, L. et al. Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor. Sig Transduct Target Ther 7, 248 (2022). DOI: 10.1038/s41392-022-01034-7