Gene therapy technique could aid islet transplants for diabetes, says Pittsb...( though the doses and the blood levels ...),Health

In the study, the researchers used a common virus called an adenovirus to deliver hepatocyte growth factor (HGF), which induces beta cell division and prolongs beta cell survival, into pancreatic islets that had been extracted from rat pancreases. Having conducted similar previous research on genetically immunodeficient mice, researchers this time sought to construct a situation that most closely mimics a human islet cell transplant according to the Edmonton protocol. They used an allogenic islet transplant system, using islets from Lewis rats and transplanting them into Sprague Dawley rats (this is similar to transplanting islets from one human donor into a different recipient). They also delivered the islets into the portal vein (as is performed in humans) instead of through a kidney capsule graft (used in their prior studies in mice). Finally, researchers used the standard combination of immunosuppressive drugs tacrolimus, sirolimus and daclizumab.

After one day, and lasting three weeks, the blood glucose control was far superior in the HGF-treated rats than the controls. Also, the number of islets surviving in the liver in rats that had been transplanted with HGF-treated islets was double that seen with controls, whose transplanted islets had been treated with a control adenovirus. These studies confirmed prior studies from the Pittsburgh group demonstrating the efficacy of HGF in enhancing islet transplant outcomes.

The experiment was then repeated, going beyond three weeks to see if the improvements would be long lasting. As had been observed previously, but this time for 18 weeks, rats whose islets had been pre-treated with HGF maintained blood glucose levels 200 mg/dl lower than the control animals. Since rats live for approximately two years, this could equate to a decade or more in a human.

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Contact: Frank Raczkiewicz
RaczkiewiczFA@upmc.edu
412-647-3555
University of Pittsburgh Medical Center
4-Feb-2004