Scott King:

Every morning first thing, I check my e-mails to see who has sent me a message after reading one of our web sites. I get several a week, trending more every week, and I always enjoy them. Part of our new model of medical research at Hanuman Medical is to become acquainted with patient advocates as well as participants in the pharma/medical venture complex. Staying in touch with people whose lives are touched by the disease quickens us here.

The most common e-mail I get in response to the Islet Sheet Medical web site is one asking if it is possible to volunteer for our clinical trials. This astounds and moves me. People I don’t know are offering their bodies in the hope that our therapy will help them and others like them. So I’d like to tell you about clinical trials of the islet sheet.

First we need to look at the genus of which the islet sheet is a species. This genus is all ways of implanting insulin-producing tissue into diabetics who need insulin. Members of this genus are classified by two things: the insulin producing tissue and the way to protected it from rejection.

Ways to implant insulin-producing tissue

Insulin producing tissue
Tissue protection human pancreas human islets of Langerhans animal islets of Langerhans engineered tissue
immune suppression
thousands
hundreds
a few
none
microcapsule  
a few
none
none
macrocapsule  
a few
none
none

The only therapy that has advanced beyond clinical trials to general clinical practice is the human pancreas allograft. Thousands have been done and the success rate is respectable. The number of pancreas transplants is limited by pancreas availability and the side effects of immune suppression, so the success rate is not growing much.

Implantation of isolated islets of Langerhans — the 2% of the pancreas that makes insulin — has been studied for years and has gradually improved year by year. I believe that medical research is making the transition from clinical trials to accepted clinical use. Signs point to a high success rate when the islets are prepared carefully and the right immune suppression is used. In this dawning era more and more pancreases will be used as a source of human islets (displacing pancreas transplants) and this procedure will become limited by availability of pancreases.

But our work is designed to move beyond those people with diabetes who are willing to tolerate all of the problems associated with immune suppression. We know that the normalized blood sugar prevents and even reverses diabetic vascular decay. So we know that we can cure all insulin using diabetics if we can find a large enough source of tissue and a better way to protect the tissue than general immune suppression.

Given this background, what is needed to perform a clinical trial with Islet Sheet Medical’s thin sheet macrocapsule bio-artificial pancreas? As with all medical devices, first safety, then efficacy.

Medical devices are regulated throughout the developed world. Specific tests are required and an application must be made to the regulatory authority. Some islet devices have been approved from clinical study by the FDA, for instance the Circe Biomedical device. Other have been implanted using local research hospital approvals. What these regulations boil down to is making sure that the device is unlikely to cause harm. ISM is fortunate that the polymer we use is already approved for implantation, and, unlike microcapsules, the sheet can be removed if something goes wrong. Thus we do not anticipate unusual concerns about the safety of our device.

So the key issue is efficacy. This is a bright spot in diabetes research. We know what a cure to diabetes looks like. Thanks to the DCCT study we are certain that euglycemia is a cure. And every diabetic knows that blood sugar is easily measured.

Another bright spot is that we can accurately simulate diabetes in animals. Simply put, if we can cure a dog of diabetes we are quite sure we can cure humans.

Consider how important this is, by comparing diabetes with AIDS. The mechanism of the disease is poorly understood even after years of research — there are no reliable surrogate markers for disease. So let’s say you have a magic pill that you claim cures AIDS. There are animal models but they aren’t very good. So you cannot be sure without clinical trials. Then, when you gave the pill in a clinical study you could not tell if it works immediately. The only way to know if you had cured it would be to follow the patients for years to make sure they did not get sicker and die!

For the islet sheet device the islet allograft sets a benchmark. Our technology merely takes these same islets and puts them into a protective jacket before implanting them. The same tests used to evaluate islet transplantation will be used to evaluate islet sheet implantation. By comparing naked islets with covered islets we will know immediately how well the islets function in the covering. We have already shown this to be true in the test tube. The next step is to prove it in animals.

So who is the lucky diabetic who gets the first implant? This decision is made at the clinical research center, not by Islet Sheet Medical’s staff! Recruitment for clinical trials varies by the therapy. Given the relative safety of the sheet I think we will have considerable latitude. (If a therapy is risky usually severely ill patients are selected.)

So if you want to be first on your block with the sheet, live in Cincinnati or Edmonton!

Scott R. King

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