Denise Faustman: To Stop Diabetes, She's Attacking the Immune System

Denise Faustman, Director, Mass General Immunobiology Lab

Her name draws sparks. Critical scientists question her methods and challenge her findings. But Denise Faustman has plenty of supporters who see her as a "tough tester of scientific hypotheses," which is how the 51-year-old Massachusetts General Hospital lab director describes herself. Feelings run high in part because the stakes are huge: reversing type 1 diabetes, projected to double in children by 2020. Faustman has done it in mice. Now she and colleague David Nathan are running a clinical trial to see if they can do it in people.

Faustman previously reported that she had cured mice with "end stage" type 1 diabetes, meaning they had lost all ability to produce insulin. A drug called CFA was a vital key to her multistep treatment. It provoked an inflammatory response that killed the immune system's rogue cells, which had destroyed the pancreatic cells that make insulin. Mice that should have been dead scampered in the sawdust, normal blood sugar restored. When they were autopsied, clusters of insulin-making cells were found in their pancreases. Stopping the autoimmune attack had let the pancreas heal, an ability previously unknown, she says.

In the current clinical trial, Faustman is analyzing blood from a small group of people with "end stage" type 1 diabetes and from healthy controls. All are receiving either a placebo or BCG, an inexpensive drug long used as a tuberculosis vaccine. Faustman believes the old drug can knock out rogue cells in people the way CFA—which is not manufactured for human use—did in her mice by triggering the same immune response. It is only a toxicity study, but Faustman will be alert for signs of pancreatic regeneration.

It's a "fishing expedition," says Jay Skyler, chairman of TrialNet, an international network of type 1 diabetes trials. He says that regenerative potential is likeliest in diabetics who retain some pancreatic function, and that in past trials, BCG didn't help and even worsened type 1 diabetes. Faustman says the drug flopped because of dosing problems and a poor grasp of how BCG works in people. She agrees there could be setbacks ahead. But not trying, she says, "is 100 percent failure."