Novel drug combination shows preclinical diabetes promise
medwireNews: Combining a glucagon-like peptide (GLP)-1 receptor agonist with an experimental compound could increase the function and numbers of beta cells, suggest preclinical findings in Science Translational Medicine.
The researchers tested drugs from the dual-specificity tyrosine phosphorylation–regulated kinase 1A (DYRK1A) inhibitor class, which have been shown to induce cell proliferation, in combination with various GLP-1 receptor agonists to provide beta-cell specificity.
They found the combination to have dose-dependent synergistic effects on beta cells from deceased donors, with the DYRK1A inhibitors having little or no effect alone, but showing a marked effect on beta-cell proliferation when given with “even trivial doses” of a GLP-1 receptor agonist. This was the case for all combinations tested, and the increased proliferation did not lead to dedifferentiation of the beta cells.
The drug combination caused proliferation of human beta cells when transplanted into mice, and normalized blood glucose in mice that received human beta cells following the obliteration of their own islets.
The proliferation induced by the drug combination “may be in a range that could allow for restoration of normal β cell mass in people with [type 2 diabetes] and [type 1 diabetes],” say Andrew Stewart (Icahn School of Medicine at Mount Sinai, New York, USA) and study co-authors.
They note, however, that many barriers remain to clinical use, including the possibility of DYRK1A inhibitors having psychoactive properties, and the potential for oncogenic effects of regenerative therapies, such as this drug combination.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group