Studying GPX-002 in Diabetic Mice and Non-Human Primates

Researchers at the University of Pittsburgh have conducted preclinical studies evaluating GPX-002 in diabetic mice and non-human primates (NHPs). The same general novel approach is used in each of Type 1 and Type 2 diabetes whereby an AAV vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, we believe this can be done with a routine endoscopy procedure.

Reversed Drug-Induced Diabetes in T1D Toxin-Induced Mouse Model

In studies in mice treated to destroy insulin producing beta cells and in non-obese diabetic (NOD) mice, both of which are models of Type 1 diabetes, our gene therapy approach restored normal blood glucose levels for an extended period of time, and markedly increased the mass of insulin producing beta cells.

The figures below show that starting approximately one week after injection of the engineered AAV construct (labeled AAV8-PM) into the pancreatic duct, the blood glucose level markedly improved in mice in which insulin producing cells had been destroyed by the drug alloxan (ALX). In addition, the mass of beta cells and beta-like cells producing insulin was significantly increased.

Restored Blood Glucose in T1D In Autoimmune Mouse Model for Four Months

In vivo mice studies have found that GPX-002 restored normal blood glucose levels for an extended period of time, which lasted approximately four months. According to the researchers, the duration of restored blood glucose levels in mice could translate to decades in humans.

Induced Generation of Functional Insulin-Expressing Cells from Alpha Cells in Human Islets

The researchers also carried out an experiment to determine if the same AAV engineered construct could be used to convert human alpha cells to beta-like cells that would produce insulin, as shown in the figures below. Human pancreatic islets were treated with streptozotocin (STZ) to destroy beta cells, and then were treated with the AAV engineered construct. They were then transplanted into NOD mice that had been treated with alloxan (ALX), and also modified so they would not reject human cells. The NOD mice that received the AAV engineered construct had significantly lower blood glucose levels and higher mass of beta and beta-like cells that secrete insulin than did control mice. These data suggest that the same AAV engineered construct can convert human alpha cells into insulin secreting beta-like cells.

This data provides a potential basis for further investigation in human Type 1 diabetes.

Advanced Technologies & Treatments for Diabetes (ATTD 2023)

In February 2023, research collaborators at the University of Pittsburgh presented preclinical data in a NHP model of Type 1 diabetes highlighting the therapeutic potential of GPX-002 at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2023) in Berlin, Germany. 

The statistically significant study results showed the treated animals had:

• Decreased insulin requirements
• Increased c-peptide levels
• Improved glucose tolerance compared to baseline

KOL Event: Novel Gene Therapy to Treat Type 1 Diabetes

In April 2023, Genprex hosted a Key Opinion Leader virtual event entitled “Novel Gene Therapy to Treat Type 1 Diabetes,” which discussed preclinical data reported at ATTD 2023 supporting gene therapy to treat Type 1 diabetes. Watch the KOL event here.

We believe the data in NHPs demonstrate the potential for this gene therapy treatment to eliminate the need for insulin replacement therapy for Type 1 and Type 2 diabetic patients.

To learn more about scientific evidence and studies supporting GPX-002 and the Pdx1/MafA genes, please refer to our Pdx1/MafA Bibliography page.