JDRF-funded researchers in Canada and Massachusetts have stimulated the birth of new insulin-secreting beta cells by treating human islets with a mixture of two naturally occurring peptides: epidermal growth factor (EGF) and gastrin.
The treatment caused primitive “precursor” cells in the islets – known as ductal cells – to develop into beta cells, increasing overall beta cell mass and boosting insulin levels within the islets. In fact, according to these new research findings, this form of combination therapy can boost beta cell numbers as much as threefold. This achievement represents an important step towards learning to regenerate beta cells in people with diabetes. The report will be covered in the June issue of Journal of Clinical Endocrinology and Metabolism, and is currently posted on the Journal’s website.
This combined-drug approach to creating beta cells essentially recreates the process by which beta cells are normally formed during fetal development. This phenomenon, called islet neogenesis, usually stops at birth. The therapy works in two stages: EGF (given in low levels) causes islet precursor cells to multiply in the first stage, and then gastrin (given in high levels) causes the precursor cells to differentiate until the cells are mature beta cells. The growth factors are not effective unless they are given in combination, and the beta cell neogenesis does not run rampant—it stops when the injections stop, which means that doctors should be able to control the growth.
According to Dr. Richard Insel, Executive Vice President of Research for JDRF, “Beta cell regeneration is one of JDRF's major goals because it could provide the ability to restore beta cell function without transplantation, which requires a source of islets. The new published results are exciting and provide evidence of the effect of this therapeutic combination on human beta cells.”
The findings result from the work of Alex Rabinovitch, M.D., Wilma Suarez-Pinzon, and Jonathan Lakey at the University of Alberta in Edmonton, who conducted the study in conjunction with Stephen Brand, M.D., Ph.D. of Waratah Pharmaceuticals in Woburn, Massachusetts. Funding for this research came from JDRF, Waratah Pharmaceuticals, and Transition Therapeutics.
Based on this most recent success, human trials will begin later this year to see if the treatment can help patients regain at least some of their insulin-secreting function. In these trials patients will receive injections of the two growth factors once or twice a day for several weeks to spur new beta cell growth. Although it is not clear how long the new beta cells will remain, the researchers hope the procedure will allow patients to regain some of the insulin-secreting function lost from the disease.
The upcoming clinical trials in type 1 patients will use analogues of EGF and gastrin and will be conducted by Transition Therapeutics, which merged with Waratah Pharmaceuticals in 2002. The company received FDA approval in January to test the combination in type 2 patients in a separate clinical trial.