Breakthrough Gene-Edited Islet Transplant Succeeds in Diabetes Patient

Researchers led by Uppsala University Hospital have announced that gene-edited donor islet cells remained viable for 12 weeks inside a man with long-standing type 1 diabetes without requiring immunosuppressive medication.

Intensive insulin treatment can delay complications and increase life expectancy, but early-onset type 1 diabetes is still associated with lower quality of life, higher cardiovascular risk, and reduced lifespan. Additionally, the toxicity from lifelong immune suppression contributes to increased morbidity and mortality among organ recipients.

The study, "Survival of Transplanted Allogeneic Beta Cells without Immunosuppression," published in the New England Journal of Medicine, involves a first-in-human open-label trial testing whether hypoimmune-engineered islet cells could avoid rejection.

The trial included a single 42-year-old man with type 1 diabetes for 37 years.

Islets from an O-matched deceased donor pancreas were isolated, dissociated, edited using CRISPR-Cas12b to knockout B2M and CIITA genes, lentivirally transduced to overexpress CD47, reclustered, and injected into the left brachioradialis muscle in 17 tracks under general anesthesia. No glucocorticoids, anti-inflammatory drugs, or immunosuppressants were administered.

Over 84 days, serial assays revealed strong adaptive and innate immune responses against residual wild-type and double-knockout cells, while hypoimmune cells showed no T-cell activation, antibody production, or cytotoxicity. High-sensitivity C-peptide levels remained near or above 10 pmol/L and increased during mixed-meal testing; glycated hemoglobin decreased by approximately 42%. Magnetic resonance imaging and GLP-1 receptor-targeted PET scans confirmed viable grafts with no inflammation. Four mild adverse events were recorded, none related to the treatment.

The daily insulin regimen continued as only 7% of a full replacement dose of beta cells was implanted. The study authors consider this trial a proof-of-survival and proof-of-function validation.

Researchers propose that hypoimmune gene editing could potentially lead to a curative beta-cell replacement therapy for type 1 diabetes without systemic immune suppression, offering hope for improved daily management and reduced long-term complications for millions of patients.

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