Islet Sheet Technology – Hope for Diabetes Cure

Scott King, pioneer diabetes biotechnology analyst, and founding President of Cerco Medical, is determined to find a cure for diabetes.

Scott King, Hong Kong, March 2010

More specifically, Scott is leading the development of a new technology that will provide stable blood glucose levels without injected insulin or immunosuppressive drugs. The technology is based on a removable, bio-invisible sheet called an Islet Sheet and research is ongoing now at the University of California, Irvine (UCI).   The research project’s name is the Solving Diabetes Project, and funding is provided by the Hanuman Medical Foundation.

When Scott recently visited Hong Kong en route to his home in San Francisco, I had the opportunity to ask him a few questions about this research, and how it might change the way people with type 1 diabetes manage blood sugar control in the future.

It’s probably worth mentioning that Scott has type 1 diabetes too.

Why name it the Solving Diabetes Project?
The Solving Diabetes Project name was chosen to communicate that this is not an open-ended attempt to seek some ill-defined goal. We are problem-solving and the problem is type 1 diabetes. We have a plan, namely to get our Islet Sheet into clinical studies and on the market. The Islet Sheet exists, it is not a mere concept or notion. The sheet will succeed or fail in the coming months, and if it fails we will stop. In this field that plan makes us stand out.

The Solving Diabetes Project is based on islet transplantation. Historically, why has “cell therapy” held so much promise for type 1 diabetes?
Diabetes management is perfect delivery of insulin. That is it. And islets do that best. In fact they do it perfectly. So I have always thought islet transplantation was the way to go. In 1980, as a newly diagnosed diabetic, I was given the opportunity to write an investment report on the future of diabetes therapy. Autografts — where rejection is not an issue — were already known to normalize blood sugar. So I predicted in 1980 (in writing!) that the cure of diabetes would be islet transplantation without drugs. And the two ways to transplant without drugs (in 1980) were tolerance induction and encapsulation. So 30 years later tolerance induction remains on the distant horizon and encapsulation is here now.

All the variations of islet transplantation are the same. Get the islets into the diabetic host and let them do their work. They need a good supply of nutrients and the need to be protected from rejection. Pancreas transplantation has its uses when you are transplanting a kidney too but for most diabetics islets are best. And the side effects of drugs in conventional islet transplantation are worse than diabetes, so the drugs must be eliminated with encapsulation technology.

Can you describe Islet Sheet Technology in a little detail, especially for those of us without a hard science background?

The Solving Diabetes Project - an Islet Sheet

The Islet Sheet looks like a clear business card and feels wet and slick on the finger. You can see the islets, which look to the naked eye like fine white sand. Each sheet has about 100,000 islets, so a human would need about five Islet Sheets. In addition to human, pig or stem cell islets the sheet is made from a calcium gel of a polymer we make from California kelp. It is really slick — surgeons admire it. We are not sure the best implant location. We are putting it under the skin now, and we also intend to place it in the abdomen so the insulin will go to the liver, just like healthy islets.

We believe that the Islet Sheet will make exactly enough insulin to control blood sugar, and will require periodic replacement, perhaps every two years. Fortunately the Islet Sheet can be retrieved and replaced, which makes our technology safer than any other encapsulation system. This safety is attractive to potential corporate partners.

What was the tipping point for you to believe in the encapsulation of islet cells as the way forward?
The tipping point for me was in the 90’s when we cured a dog with encapsulated dog islets at UC Davis. The dog did not need insulin for five years. The microcapsules were made by Randy Dorian, and the islets by Jonathan Lakey, amazingly the team that is leading work on the Islet Sheet twenty years later! In all the years of frustration while this project did not getting proper funding, that dog kept giving me hope.

Can you talk about the current research team working on the Islet Sheet? If you had to stage the work from beginning to end – where has the project been and where is it today?
We have three success points. The third is clinical success in human studies. The second is success in large animal studies. The first, which we are winding up now, is refinement of the Islet Sheet to assure minimal foreign body reaction and proof of retrievability.

The team is focused on Jonathan Lakey’s new islet research center at UC Irvine. The decision of the University of California to start a world class islet research group and to hire professor Lakey to lead it is the most important reason we are working on this cure again. (Jon is, in the opinion of many, is the best man in the world at islet isolation.) We worked with Jon when he ran the human islet laboratory at University of Alberta, and he was very excited about the results we were seeing in Edmonton. His move to California has simplified the logistics and the fund raising. In addition to Jon, there are about five scientists working full or part time on the Islet Sheet at UCI, and growing.

The invention team (three of us) works in Irvine to make Islet Sheets but mostly in San Francisco at our corporate lab. The kelp is harvested in San Diego and processed in San Francisco. Methods development and physical evaluation of the sheets is in San Francisco.

Can you discuss any political, ethical or regulatory obstacles associated with the Islet Sheet and encapsulation technology?
Maybe I’m Pollyanna but at this point I don’t see many political, ethical or regulatory obstacles. At least for our first clinical trials which will use human islets, like the Edmonton protocol. These islets are regulated by the FDA already, so we need only show that the sheet itself is safe. Certainly the situation at UC Irvine could not be better — we are getting enthusiastic support from the top to the bottom of the Irvine branch of the University of California.

Longer term we will need a massive source of islets. The people of California are investing billions of dollars in islets from stem cells and that may work out. Mid term we look to pig islets, and fortunately there is a supplier of clinical-quality islets in New Zealand. The political, ethical and regulatory obstacles that Living Cell Technologies (New Zealand) faced there took years to resolve but they are now conducting human studies with encapsulated pig islets. We need only replace their current microcapsule system with the Islet Sheet.

What is the difference between a functional cure and a cure for type 1 diabetes? How does Islet Sheet technology compare with other functional cures on the horizon, like the artificial pancreas.
The Hanuman Foundation decided to call the Islet Sheet a functional cure because there are many people who look to islet regeneration as the true cure. I actually agree that regeneration could be superior to the Islet Sheet, but my own view based on the immunology of T1 diabetes and the developmental biology of islets is that we do not have the technology required, and won’t in my life time (and I intend to live decades more). So the Islet Sheet is a functional cure — BGs will normalize with a technology that will require some maintenance but not drugs.

The JDRF promotion of the artificial pancreas is a puzzle to me. I have studied diabetes physiology. You can prove on a single sheet of paper that it cannot work.   Ever.   I was told by a bioengineer working on Al Mann’s $100 million team that they had proven that it cannot work. I don’t know a single scientist or clinician in diabetes — and I know a lot – who think the artificial pancreas will cure diabetes.

On the other hand JDRF funding of encapsulation is tiny, and what they are funding has no utility in our view, but is rather academic. They don’t show any interest in what we are doing. So if you like encapsulated islets, send your money to the Hanuman Medical Foundation, not the JDRF!

Let’s move forward in time. The Islet sheet has succeeded all clinical trials, and has been approved for patients. Can you walk me through my new life with the Islet Sheet?
A few months ago your Islet Sheets were implanted in a minimally invasive outpatient procedure. You tapered your insulin while measuring BGs and in a few days injected insulin was down to zero. These days, about twice a week, you check a postprandial glucose, and depending on the meal, might find 80 to 140. You are aware that some time in the coming months, depending on your islet dose, that your post meal glucose will start to drift up and you will be evaluated for Islet Sheet supplementation or replacement. Then you might have another minimally invasive surgery and a supplemental (next generation!) sheet implanted.

So your life changes from managing insulin minute-by-minute to managing your Islet Sheet month-by-month. And BGs will be much better. And your risk of hypoglycemia near zero.

It’s difficult not to become excited about this technology, so what’s holding it back?  What is the greatest challenge the project faces today?
We are starting large animal studies. One diabetic pig study can cost $35,000. So we need more money that we have been spending. Once we have large animals cured the Foundation will have an easier time of it, but for now it is a challenge.

For more information, or to make a donation to the project:
Go to the Hanuman Medical Foundation to learn more about “orphan therapies” and the Solving Diabetes Project.  You can also contact Paul Del Bene, Director of Advancement for the Foundation at paul@hanumanmedicalfoundation.org