New Drug Could Revolutionize Treatment of Congenital Hyperinsulinism

“It’s like the opposite of diabetes.” That is the simplest way to explain congenital hyperinsulinism (HI), a rare disease in which the pancreas makes too much of the hormone insulin, causing blood glucose to plummet. Depriving the brain of the sugars it needs to function can damage it quickly, so identifying and monitoring kids with HI is urgent and active work.

More than 400 patients with HI have been evaluated and treated at CHOP’s Congenital Hyperinsulinism Center. The center’s expertise is so renowned that it draws children with HI from around the world.

“CHOP is the only center in the USA that has a multidisciplinary team dedicated to caring for these children and doing research to improve the management of their condition,” says center director Diva De León, M.D.

Currently, about half of HI cases can be treated with medication or cured by surgically removing portions of the pancreas. The CHOP team performs 18F-DOPA PET scanning, an innovative imaging technique that helps surgeons pinpoint abnormal tissue and focal lesions, sparing healthy cells in the pancreas, significantly reducing the risk of diabetes in patients with focal HI, and potentially leading to a cure. This technology can reduce unnecessary near-total pancreatectomies.

However, for some patients the only option is to remove most or all of the pancreas. De León and her colleagues believe this is an imperfect solution and they are investigating an alternative approach that could revolutionize treatment for HI: a new drug that can help manage glucose levels in even the most severe forms of the disease — without surgery.

It builds on a decade of research by De León to understand how insulin-secreting pancreatic cells work. Armed with that knowledge, she ultimately zeroed in on an investigational drug called exendin-(9-39), which showed success in decreasing insulin production in mice. Exendin-(9-39) is a modified form of exendin-4, a synthesized version of a protein derived from Gila monster saliva that is currently used to treat diabetes.

The results of De León’s clinical trial, the first using this drug in humans, were published in the journal Diabetes. They showed that exendin-(9-39) successfully increased fasting blood glucose and inhibited insulin secretion in nine patients. This study provides proof of concept that will allow for larger studies in the future and hopefully FDA approval of the medication. The center is preparing an expanded clinical study for 2014.