Time for a Cure

Ever since I developed type 1 diabetes in 1977 I have been looking for a cure. Lately, I have come to believe that our work at Islet Sheet Medical will produce one very soon. But today I declare to you all that, even if we here fail, I believe that some one will succeed soon.

Why such hope after twenty years? First, the success of our friends at the University of Alberta has demonstrated that islet transplantation can cure the disease (at the price of immune suppression). The success rate, defined as being free from the need for insulin injections, is turning out to be about 80%, which is the success rate of other organ transplants such as kidney and liver. Drs. Shapiro, Lakey and their colleagues have transformed islet transplant from "extraordinary" to "routine" organ transplant. It is only a matter of time before their results are repeated at other islet transplant centers. Then multiple centers will develop the infrastructure to collect and distribute human islets and many more people will be cured with the "Edmonton protocol." Of course they will put up with expensive immune suppression drugs, but their metabolic cure is hope for us all.

Another reason to hope is that we know what the cure for diabetes looks like, and can determine whether we have found it This may sound odd, so let me explain. When I developed diabetes many researchers thought that diabetes is in essence a vascular disease with a metabolic component. After all, the damage to people with the disease takes the form of vascular decay, and it is not obvious that the elevated blood sugars cause or are even related to the vascular problems. As most of you know, many studies capped by the DCCT study have together demonstrated that better metabolic control, i.e., better blood sugars, conclusively leads to less vacular damage. It is quite clear that euglycemia is the cure for type 1 diabetes. Good blood sugar all the time is a cure. It follows that a therapy that produce good blood sugar minute-to-minute is a cure for type 1 diabetes.

And we know how to make good blood sugar: just the right amount of insulin minute-to-minute! Everyone's efforts are now focussed on this clear bur fairly elusive goal. I call insulin replacement therapies that deliver insulin exactly when needed "smart" therapies. The following tree shows all the smart therapies. The colors are my handicapping for success.

Therapies that are proven to work are blue. The one proven "smart" therapy is islet transplantation by the "Edmonton protocol". Its major drawbacks are the need for drugs and the shortage of islets of Langerhans.

The alternative to drugs is to protect the islets of a membrane. All the problems that have bedeviled this approach over the past 25 years have in common that they are relate to making nutrients available to the islets so that they can thrive and make insulin exactly when needed. Two approaches to bring the blood to the islets, the vascular shunt (blood flows through the device) and neovascularization (an outer membrane that attracts blood vessel formation) have been shown to fail. But the other approach -- passive diffusion -- is showing promising results in more than one center. Researchers at the Joslin Clinic led by Gordon Weir are showing promising results with small capsules. Dr. U. Zimmermann of the Biozentrum of the University of Würzburg is showing promising results with their ultrapure alginate capsules. Another leading researcher is Dr. Riccardo Calafiore of the University of Perugia. One or more of these efforts will succeed soon.

Our work on the islet sheet is similar in that we rely on passive diffusion to feed our islets. Recently we have demonstrated that the sheet survives for weeks without provoking significant fibrosis, a significant advance. We are looking forward to large animal experiments.

Another approach that has moved from large animal work to clinical studies if the biomechanical pancreas. Here the insulin is provided by a pump run by a digital computer. The computer's program depends on input from a glucose sensor. Much progress has been made recently, especially Minimed Inc.'s work on continuous glucose monitoring, and clinical studies show how far these researchers have come.

Scott King

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