Detecting Cell Loss in Diabetes

A novel molecular tracer could help doctors track the loss of insulin-producing cells in diabetes. Such a tool would allow both doctors and drug developers to better assess the effectiveness of new treatments. It could also shed light on the disease by allowing scientists to correlate loss of insulin-producing cells with diabetes symptoms for the first time.

“If we could see cell loss early, perhaps we could get patients started on therapy before there is irreversible damage,” says Dan Skovronsky, founder and CEO of Philadelphia-based Avid Radiopharmaceuticals, the company that is developing the marker.

Type 1 diabetes and late-stage type 2 diabetes are characterized by the loss of the insulin-producing cells in the pancreas. Scientists estimate that people diagnosed with type 1 diabetes have already lost approximately 50 to 90 percent of their insulin-producing cells by the time they begin to show symptoms. “Insulin measurements are only reliable when it’s too late–when the disease is well advanced,” says Paul Harris, a biologist at Columbia University, in New York. “Patients are losing cells silently.”

Because these cells are relatively rare in the pancreas, tracking them in patients has historically been difficult. “They only make up about 1 percent of the cells in the pancreas, so you really need something molecularly targeted to see them,” says Skovronsky.

Avid’s marker, originally developed by Hank Kung, a scientist at the University of Pennsylvania, in Philadelphia, shows promise in animal studies. It binds to a receptor on the surface of the insulin-producing cells; the marker is tagged with a radioactive label so that it can be detected using positron emission tomography, or PET imaging. This type of imaging is currently used to locate tumors and assess brain and heart function.

The marker can successfully distinguish between the pancreases of healthy rats and those whose insulin-producing cells have been destroyed, according to results presented at the Society of Nuclear Medicine’s annual meeting in Washington, DC, earlier this month. Kung now plans to test the marker in additional animal models of diabetes to show that it can track more-gradual changes in the number of insulin-producing cells, as is likely to occur in human diabetes.

The researchers say that pharmaceutical companies have already expressed interest in using the marker in clinical trials of new drugs designed to regenerate insulin-producing cells.

The test might also help identify at the earliest stages those at risk of diabetes, such as people with a family history of the disease and pregnant women with other risk factors for gestational diabetes–in other words, people who might benefit from protective therapies currently in development.

The PET marker was originally developed to target brain cells, and it’s now in early-stage clinical trials for people with neurodegenerative disease. (For reasons not yet clear to scientists, brain cells and pancreatic cells share many molecular markers.) Skovronsky says that testing for diabetes is likely to move forward quickly because the compound has already gone through safety studies and has regulatory approval from the FDA. Avid aims to begin diabetes testing this year.