May 14, 2026 —
Genprex announced positive preclinical data for its diabetes gene therapy candidate, Pdx1/MafA gene therapy, also known as PM or GPX-002, at the 2026 American Society of Gene and Cell Therapy Annual Meeting. The data, presented by Genprex’s research collaborators, showed that pancreatic delivery of an AAV8-based Pdx1/MafA gene therapy reversed hyperglycemia in preclinical mouse models of type 2 diabetes within four weeks.
Type 2 diabetes is characterized by insulin resistance and progressive pancreatic beta-cell dysfunction. While current therapies can help manage blood glucose, many do not directly restore beta-cell function. Genprex’s approach is designed to address this underlying disease biology by delivering the transcription factors Pdx1 and MafA, which play important roles in beta-cell identity, maturation, and insulin-producing function.
In the study, male C57BL/6 mice were maintained on either a regular diet or a high-fat diet for 24 weeks to induce type 2 diabetic features. High-fat diet mice then received retrograde pancreatic duct infusion of AAV8 vectors encoding Pdx1 and MafA under either the CMV promoter for broader islet-cell targeting or the rat insulin promoter for beta-cell-specific targeting. Control groups received either no procedure or a control virus, while diets remained unchanged after surgery.
Four weeks after treatment, mice receiving PM gene therapy showed major improvements in diabetes control. Islets isolated from high-fat diet mice treated with CMV-PM-GFP demonstrated glucose-stimulated insulin secretion comparable to islets from regular-diet mice and higher insulin secretion than control high-fat diet groups. Importantly, beta-cell-specific delivery using RIP-PM-GFP also reversed hyperglycemia and improved ex vivo glucose-stimulated insulin secretion, suggesting that enhanced beta-cell function is a key driver of the therapeutic effect.
Additional analyses supported beta-cell restoration. Electron microscopy showed that PM treatment increased total and mature insulin granules while reducing immature insulin granules compared with high-fat diet controls. Single-cell RNA sequencing and pseudotime analysis further suggested a shift of beta cells from an immature state toward a more mature functional state after treatment.
The findings suggest that AAV-mediated Pdx1/MafA delivery may reverse hyperglycemia by improving beta-cell maturation and insulin secretory function. Genprex also noted that the pancreatic delivery approach could be technically translatable to humans using endoscopic retrograde cholangiopancreatography. While the program remains preclinical, the data highlight a potential gene therapy strategy for type 2 diabetes that moves beyond chronic glucose management toward restoring endogenous beta-cell function.
