Breakthrough in Gene-Edited Islet Transplant Demonstrates Success in Human Trial

Researchers at Uppsala University Hospital have achieved a significant milestone in diabetes treatment by demonstrating the survival and function of gene-edited donor islet cells in a human patient without the need for immunosuppressive drugs. The study, published in the New England Journal of Medicine, involved a 42-year-old man with a 37-year history of type 1 diabetes. Islets from a deceased donor pancreas were genetically modified using CRISPR-Cas12b to remove B2M and CIITA, proteins involved in immune recognition. These hypoimmune islet cells were also engineered to overexpress CD47, a protein that helps evade immune system attack. The cells were transplanted into the patient’s arm muscle in 17 separate sites without administering any immunosuppressive medications. Over 12 weeks, the transplanted cells showed signs of viability and function through various imaging and biochemical tests, including stable high levels of C-peptide and a 42% reduction in glycated hemoglobin levels, indicating improved blood sugar regulation. Despite immune responses targeting residual unmodified cells, the hypoimmune cells triggered no T-cell activation or antibody production, demonstrating their immune evasion capabilities. The patient continued insulin therapy but required only a small fraction of the typical dose, highlighting the potential of these gene-edited cells as a sustainable treatment option for long-term diabetes management. The study's findings suggest that hypoimmune gene editing could pave the way for universal, immune-compatible beta-cell replacements that eliminate the need for lifelong immune suppression, thereby improving quality of life and reducing complications for individuals with type 1 diabetes.