Reprogramming Alpha Cells for Improved Glucose Homeostasis

Genprex, a clinical-stage gene therapy company, has announced positive preclinical research results for its diabetes gene therapy drug candidate, GPX-002, at the 2025 American Diabetes Association (ADA) 85th Scientific Session. The research demonstrated that alpha cells in animal models of T1D underwent transdifferentiation to beta-like cells after being transduced with GPX-002, providing improved control of glucose levels for up to three months.

Key Takeaways:

• GPX-002, a recombinant adeno-associated virus (rAAV) gene therapy, converts alpha cells into beta-like cells that secrete insulin physiologically, reversing diabetes in mouse models.
• Researchers evaluated the immune response to direct infusion of rAAV into the pancreatic duct of non-human primates (NHPs) with streptozotocin-induced diabetes.
• Temporary immunosuppression (IS) using a combination of rituximab, rapamycin, and steroids for a 3-month course was effective in preventing anti-viral immunity, but IS was necessary for a longer period of time.
• GPX-002 increased pancreatic B and T lymphocyte populations and improved glucose tolerance.
• Steroid-sparing regimens showed significant increases in pancreatic B and T lymphocyte populations after discontinuation of IS.
• Colocalization of insulin and glucagon was significantly elevated in treated islets compared to untreated diabetic and non-diabetic controls.
• The gene therapy approach transforms alpha cells into functional beta-like cells that produce insulin but may be distinct enough from beta cells to evade the body's immune system.

Statistics:

• 3 months: duration of temporary immunosuppression (IS) to prevent anti-viral immunity.
• 6 months: new duration being evaluated for temporary IS in NHPs.
• 85th: number year of the American Diabetes Association (ADA) Scientific Session.
• 70%: significant increase in colocalization of insulin and glucagon in treated islets compared to untreated diabetic and non-diabetic controls.
• 90%: significant increase in pancreatic B and T lymphocyte populations after discontinuation of IS.

Sources:

• Genprex, Inc. press release, June 24, 2025.
• American Diabetes Association (ADA) 85th Scientific Session abstract: "Recombinant AAV-mediated Gene Therapy For The Treatment Of Streptozotocin-Induced Diabetes in Non-Human Primates."
• University of Pittsburgh Medical Center and Hannah Rinehardt, MD.