Type 1 diabetes cured in mice

According to the Center for Disease Control, 1.25 million people suffer from type 1 diabetes in the US alone. So far, it can only be managed with diet and regular doses of insulin, but scientists at UT Health San Antonio have invented a way of curing the disease in mice that may one day do the same for humans even with type 2 diabetes.

Type 1 diabetes is a particularly unpleasant condition. It occurs when the pancreas ceases to produce the insulin needed by the body to metabolize sugar and, until the invention of artificial insulin injections, it was as deadly as cancer. Type 2 is the less severe form of the disease, where the body produces insufficient insulin; it can often be managed through diet alone.

Surprisingly, diabetes is an autoimmune disease. Insulin is made by specialized cells in the pancreas, called beta cells, and sometimes the body's immune system turns against itself and attacks these beta cells, destroying them. Diabetes results when this destruction is over 80 percent.

Invented by Bruno Doiron and Ralph DeFronzo, the UT Health technique uses gene transfer to alter cells in the pancreases of mice to make them think they're beta cells and start making insulin. This involves taking selected genes from external beta cells and using viruses as carriers to move them into the new host cells, in the diabetic pancreas.

According to DeFronzo, the altered cells then produce insulin, but only in the presence of sugar, which is how a functioning beta cell is supposed to work. Otherwise, the cells would just keep cranking out the hormone, metabolizing all the sugar in the bloodstream and causing hypoglycemia.

Only about 20 percent of the lost cells need to be replaced, but if new beta cells are simply introduced, it's likely that the body would attack and destroy them as well. One big advantage of this technique is that it works around the autoimmune system, which ignores the altered cells.

"If a type 1 diabetic has been living with these cells for 30, 40 or 50 years, and all we're getting them to do is secrete insulin, we expect there to be no adverse immune response," says DeFronzo.

The team emphasizes that there is a large gap between curing diabetic mice and achieving the same in human beings. They say that they'd like to start clinical trials in three years, but more animal testing is needed first at a cost of about US$5 million, as well as making an application to the US Food and Drug Administration for investigational new drug approval.

"It worked perfectly," says Doiron. "We cured mice for one year without any side effects. That's never been seen. But it's a mouse model, so caution is needed. We want to bring this to large animals that are closer to humans in physiology of the endocrine system."