The End of Diabetes: The Eat to Live Plan to Prevent and Reverse Diabetes

Researchers at Northwestern University have devised a new way for protecting transplanted islet cells from the body’s immune system.  The technologists hope to combine immunosuppressive drugs with targetted nanocarriers, protecting transplanted islet cells without impacting the wider immune system. The remedy could be a solution to one of the last major obstacles to a functional remedy for type 1 diabetes.

The technique has been used successfully in mice, and is undoubtedly many years away from large-scale deployment in humans, if it ever gets that far. Nevertheless, we applaud any progress made towards a cure for type 1 diabetes.

The problem with Islet Cell Transplants

We already know that islet cell transplantation works: patients that receive transplants of healthy insulin-producing cells achieve significantly improved blood glucose profiles. Some have even been insulin-independent for years.

So why aren’t islet cell transplantations common? Why isn’t this “cure” widely available? At the moment, there are two problems with the technique.

The 1st problem is that healthy islet cells are not easy to come by. To date, the vast majority of transplantees have received their new cells from the pancreas of a deceased organ donor, and organ donors are scarce. The treatment is basically limited to patients with a dire need—for example, those with extreme glucose management challenges, hypoglycemia unawareness, or advanced kidney disease. (And it is almost completely unavailable in the United States).

The second problem is that transplanted islet cells do not reverse the fundamental autoimmunity that causes type 1 diabetes in the first place, and even if they did, they would still be attacked by the body’s immune system. These new cells currently require to be protected by immunosuppressive drugs, drugs that can come with hefty side consequences. Some people with well-controlled diabetes worry that the cure will be worse than the condition.

The first problem, islet cell availability, appears to have been solved through the miracle of stem cell technology. At least two biotech firms, Vertex and ViaCyte, have learned how to turn pluripotent stem cells into insulin-producing islet cells. If these techniques prove to be as easily scalable as they’re reported to be, doctors will have new and abundant sources of islet cells for transplantation – no more need to wait for an organ donor.

The second problem is thornier, and researchers are working on several different approaches to avoid the heavy side effects of traditional immunosuppression therapy. Although the first Vertex patient reportedly tolerated his anti-rejection drugs extremely well, both Vertex and ViaCyte are working on methods of encapsulating transplanted cells, using physical barriers that will preserve those cells from the immune system but allow them to sense blood glucose levels and distribute insulin.

Enter the Nanocarriers

Here’s where the Northwestern University breakthrough comes in. As described by Northwestern Now, the researchers have devised a way to change the action of the common and potent immunosuppressant rapamycin. Rapamycin is a fascinating and very important drug, but it just isn’t perfect for islet cell transplantees. A low dose of rapamycin, which is customarily taken as a pill, is not enough to protect islet cells, but a larger dose has undesirable consequences, impeding the T cells’ ability to fight off regular infections and leaving the patient immunocompromised.

The Northwestern team has combined rapamycin with a targetted nanocarrier that delivers smaller amounts of the immunosuppressant exactly where it’s needed. The new treatment targets antigen-presenting cells, which essentially tell T cells where to attack. The chemistry is complex, but the result is that instead of suppressing all of the body’s T cells, the treatment instead induces the T cells to tolerate the transplanted islet cells. Rapamycin delivered in this manner should be just as effective, but require smaller doses and trigger fewer side effects.

The new results, published in the most recent edition of the journal Nature Nanotechnology, show that diabetic mice that received the nanocarrier-rapamycin mixture were essentially cured of their diabetes, and that they had a better immune response than mice treated with a standard oral dose of rapamycin.

Much work remains to be done, and of course we know that diabetes has been cured in mice many times before. The researchers are now looking for corporate partners to help them gear up for human trials. While years of work stand between this successful rodent trial and experiments in human beings, the breakthrough remains encouraging.

Diabetes Daily

The End of Diabetes: The Eat to Live Plan to Prevent and Reverse Diabetes