Researchers at Harvard Medical School have shown that switching off a single gene, ALDH3B2, can push pancreatic ductal cells toward becoming insulin-producing beta cells. The study, led by postdoctoral researcher Jian Li and published in Science Translational Medicine, used a genetic screen to find the gene. In experiments on human cells in a dish, silencing ALDH3B2 raised the rate of spontaneous conversion from under 1 percent to about 8.5 percent.
After transplanting the engineered cells into diabetic mice, the researchers detected human insulin in the animals' circulation and saw blood glucose drop to near-normal levels for six weeks. The approach differs from other emerging treatments, such as a clinical trial that equips muscle cells with insulin-making genes or efforts to grow beta cells in the lab and transplant them. Reprogramming cells already in the pancreas could avoid some immune risks, but the study's authors caution that ALDH3B2 is active in many tissues, so any therapy would need to be precisely targeted.
Li said the next step is to verify how the gene drives the transformation, then pursue either gene therapy or small molecules that inhibit the gene. Even a partial improvement could matter for the estimated 830 million people with diabetes worldwide, but the findings are early and significant technical hurdles remain before this could become a commercial therapy.