Treatment Progress in Type One Diabetes
I tend to write mostly about type 2 diabetes, because that's what I know best. But lately, there have been some interesting developments that may lead to real cures in people with type 1, so I thought I'd switch gears for a bit and write about type 1.
Classic type 1 diabetes is an autoimmune disease. Your immune system attacks your beta cells and destroys them.
Normally, the body is able to distinguish between "self" and "nonself," and it leaves your own tissues alone. How it does this is incredibly complex, and no one understands it fully yet. Cells called regulatory T cells, often abbreviated to Treg, may play an important role.
For some reason, in some cases the system goes awry, and your immune system starts attacking your own cells. If it attacks the insulation around your nerve cells, you get multiple sclerosis. If it attacks your joints, you get rheumatoid arthritis. If it attacks your beta cells, you get type 1 diabetes.
Scientists can transplant beta cells into an animal or a human being with diabetes, but the immune system will just destroy those new beta cells the same way they destroyed the old ones, especially if the transplanted cells come from another person or from a different species. The transplantation protocol called the Edmonton protocol used a cocktail of immunosuppressive drugs to try to protect the transplanted beta cells. But most of them eventually failed anyway.
One problem with this type of approach is that it takes the beta cells from two cadavers to provide enough material for one patient. There simply aren't enough donors. A group in Israel led by Shimon Efrat has succeeded in getting beta cells to multiply in culture. This would greatly increase the supply. But human trials are not expected until 5 years or more.
Scientists are also trying to find out why the transplanted beta cells eventually stop producing insulin, as most did in the Edmonton protocol. One suggestion is that the accumulation of a protein called amyloid in the transplanted islets causes them to die. Amyloid deposits are found in most people with type 2 diabetes, and now researchers have found the same thing in transplanted beta cells in people with type 1. If they could figure out how to stop the formation of these deposits, it might benefit people with both types of diabetes.
Another approach is to encapsulate transplanted beta cells in structures that will let the relatively small insulin molecules out but won't let the larger antibodies in to destroy the cell. Scientists are working on different types of encapsulation, but so far none have been totally successful.
Another approach would be to get your own body to keep producing beta cells faster than they were being destroyed. Research in this area has focused on "stem cells," or the immature, unspecialized cells found mostly in embryos that are capable of differentiating into any cell type in the body.
However, the use of embryonic stem cells has become a political issue, and so scientists are looking for another approach. One is to try to get differentiated cells to revert to their embryonic stem cell state. Then the researchers would try to figure out how to stimulate the stem cells to differentiate into beta cells. Very recently, researchers at the University of North Carolina at Chapel Hill Medical School have announced that they have produced insulin-producing cells from skin cells. They first converted the skin cells into stem cells and then converted the stem cells into insulin-producing cells.
"Of course, there are many years of additional studies that are required first, but this study provides hope for a cure for all patients with diabetes," said John Buse, president of the American Diabetes Association.
Douglas Melton, a prominent stem cell researcher at Harvard, has recently announced another approach. He and his colleagues were able to take differentiated cells and transform them directly into beta cells without first becoming stem cells. The new technique could also be used to program defective cells that cause other diseases.
Although these studies were done in mice, the same techniques could be used in humans, and Melton is planning to start research in this area, hoping to do human trials in about five years. In the mice, injecting the new beta cells didn't totally reverse the diabetes, but it brought the blood glucose levels close to normal.
Injecting new beta cells derived from your own cells would certainly help. Your body would reject your own beta cells a lot less than beta cells from someone else, or from an animal. However, the underlying problem would remain: without immunosuppression, which can be more dangerous than diabetes, your body would attack the new beta cells just as it had the old.
If scientists could learn how to turn off the attack on the beta cells without turning off the immune system's attack on harmful infections or cancer cells, people with type 1 diabetes might be able to produce enough beta cells to avoid having to take insulin, even without tricks to make other cells turn into beta cells. Most people with type 1 diabetes are still making some beta cells; it's just that they're being destroyed faster than they're being made.
A recent study attacked this problem. Denise Faustman and colleagues at Massachusetts General Hospital in Boston reported that they had succeeded in using tumor necrosis factor (TNF) to kill the specific T cells that were destroying beta cells without killing other T cells that could fight infections and foreign tissues.
This technique had previously been used in mice and had reversed their diabetes (mice keep getting cured; when are we humans going to get a cure?), but the latest research was done in human cells in culture.
The next step is human trials, and phase 1 trials are in the works.
Oddly, although in this case TNF seemed to be the key to stopping the immune attack on the beta cells, in people with type 2 diabetes, TNF is thought to cause insulin resistance. One study has shown that TNF given early in development triggers diabetes but TNF given later in development stops it. Like so much with diabetes, the systems that control metabolism are complex.
So we can't expect a type 1 diabetes cure next month. Many people who have had diabetes for many decades say they were told when they were children that diabetes would probably be cured within 10 years. That just didn't happen. And we shouldn't get our hopes up and expect it to happen now.
But fascinating experiments like these suggest that we are closing in on the answers.