Dr. James Shapiro, codeveloper of the Edmonton Protocol and a member of the Foundation's Scientific Review Committee.

History & Progress

“The focus and commitment of the Islet Medical inventors, and the track record of their research collaborators, convinced us that this project had to be funded. And we knew that the big diabetes foundations would probably ignore it.”

—John Golenski, Executive Director, Hanuman Medical Foundation

Early Promise

Studies in the 1970s demonstrated that islet transplants cured diabetes in rats and mice. But the islets didn’t survive long. So scientists began to experiment with various methods of encapsulating islets—some of them similar to microcapsules being developed today. In the flush 1990s, several well-funded enterprises competed to make progress, trying everything from alginate capsules to coated islets placed under the skin.

A few of these efforts reached clinical trials, but none resulted in more than a month or so of insulin independence in humans. In general, most failed because researchers did not understand the complexity of the problem. They usually focused on one facet, not realizing they had to do several quite difficult things at once.

Cerco Medical (now Islet Sheet Medical) was part of the first wave of companies working on microencapsulation. Randy Dorian, a founder of ISM, was among the first to discover that hyper-purified alginate is the best polymer for the “artificial” part of the device. It gels quickly, and Cerco developed techniques to remove impurities so the alginate is biocompatible. They then set out to make microcapsules with a very thin, conforming coating. In 1993 they implanted canine islets thus coated into a diabetic dog at the University of California–Davis. The dog remained off insulin for nearly six years.

Beyond Edmonton

The Cerco team soon recognized that the ideal bioartificial pancreas should be retrievable, leading them to refocus on macroencapsulation strategies—specifically, the islet sheet concept. They manufactured prototype sheets and studied their properties, including strength, thickness, and diffusion rates. Early success led to filing their first patent application in October 1995.

Great excitement greeted publication in 2000 of the Edmonton Protocol, showing that islet transplants, done right, could almost completely normalize blood sugar levels. Though the protocol never overcame the eternal problem of autoimmune attacks leading to islet loss, it remains a milestone. And one of the key members of that project, Jonathan Lakey—an expert in islet preparation—soon after joined forces with Cerco Medical.

Both Lakey and his Edmonton cohort, Dr. James Shapiro, were enthusiastic about the potential of thin-sheet encapsulation and contributed to the productive early phase of the Islet Sheet’s development. After 2001, however, conditions in the investment environment made fundraising for the project impossible, so work was put on hold.

Enter Hanuman

When Hanuman Medical Foundation was founded early in 2007, the suspended Islet Sheet Project was selected as a model for “orphan therapies” deserving of support. At first Cerco Medical planned to renew its collaboration with the University of Alberta (Edmonton), but Hanuman’s donors sought a research relationship closer to San Francisco. Providentially, Professor Lakey was about to become Director of Research at UC Irvine.

September 2008 kicked off a fruitful collaboration between Cerco’s medical inventors and Dr. Lakey’s research team. Progress advanced quickly on several fronts: significantly improving the Islet Sheet, and conducting experiments with rats and mice. In April 2010, Dr. Lakey was awarded a prestigious UC Discovery grant, recognizing highly meritorious research that addresses California’s needs, and Hanuman added funds to that

“With the funding from the Hanuman Medical Foundation, we were given the challenge of consolidating all we knew and moving it quickly to the clinic.”

—Scott King, Islet Sheet Medical

A Quantum Expansion

By 2011 the Islet Sheet Project was ready to embark on metabolic studies with larger animals. This called for additional resources and expertise, and in a major coup, one of the world’s most distinguished diabetes researchers, Richard N. Bergman, joined the team as advisor and sponsor of the work in his own laboratory at USC.

This led to another “phase change,” as Professor Bergman and his team relocated to a new lab at Cedars-Sinai Hospital. Offsetting the pause was the great advantage of being able to consolidate several parts of the project at this venue, as well as realize significant cost savings.

The Islet Sheet Project now has the capacity to move quickly into large-animal studies and that much closer to clinical trials. On the near horizon are other major collaborators—in Europe, where islet transplantation is much advanced—and interest from “big pharma” investors. The Islet Sheet Project is poised to make the transition from a small-scale exploratory project to a diabetes research enterprise.

Takeaways

  • Islet Sheet Medical (then Cerco Medical) began working on encapsulating islets in the 1970s with notable success, eventually homing in on the islet sheet concept.
  • The Edmonton Protocol proved that islet transplants could be effective long-term if done right, but lack of funding in the early 2000s temporarily derailed the Islet Sheet Project.
  • After attracting support from Hanuman Medical Foundation and gaining important new research collaborators, the project resumed work with rapid progress, and is now poised to undertake large-animal trials.