Developing a Promising Approach to Treat Congenital Hyperinsulinism

The “opposite of diabetes” may be 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. But one CHOP physician has discovered a new drug that may change HI patients’ lives.

Of the approximately 100 children born with HI each year in the United States, half seek treatment at CHOP’s Congenital Hyperinsulinism Center. In fact, the Center’s expertise is so renowned that it draws children with HI from around the world.

“In this country, CHOP is the only center that has a multidisciplinary team dedicated to caring for these children and doing research to improve the management of their condition,” says the Center’s director, Diva De León, MD.

Currently, about half of HI cases can be treated with medication or cured by surgically removing portions of the pancreas. For the other half, the only option is to remove most or all of the pancreas. It’s an imperfect solution; many of these children will need a feeding tube to control blood sugar until they’re 5 to 7 years old, and almost all will eventually develop diabetes.

But Dr. De León and her colleagues 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 Dr. 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 Dr. 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, funded by grants from the National Institutes of Health and generous donations from the Lester and Liesel Baker Foundation and the Clifford and Katherine Goldsmith Foundation, 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.

“It is a challenge to get funding for HI drug trials because pharmaceutical companies want to develop medications that can be used in larger populations,” explains Dr. De León. “A big part of what we have been able to do is because of philanthropic support. It allows us to do the research that we’re doing.”

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