Pilot Study: Investigational Drug Shows Promise for Diffuse HI Patients

Children’s Hospital, building on a pilot study in adolescents and adults, has found that an investigational drug, exendin-(9-39), could point to the first potential medical treatment for children with the severest type of congenital hyperinsulinism. These children currently face a near-total pancreatectomy. About half of HI patients, who have diffuse disease and are unresponsive to diazoxide, could potentially benefit.

Under the leadership of Diva D. De León-Crutchlow, MD, director of CHOP’s Congenital Hyperinsulinism Center, study results showed that exendin-(9-39) successfully increased fasting blood glucose in nine patients, aged 15 to 47 years old, who had hyperinsulinism caused by mutations in potassium channels. The 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.

Exendin-(9-39) blocks the action of a hormone, glucagonlike peptide-1 (GLP-1), in beta cells. The GLP-1 receptor is currently the target of drugs that treat diabetes, using the opposite effect from that investigated in this HI study.

None of the study subjects were being treated for HI at the time of the study, but all were at risk of hypoglycemia during periods of fasting. In all nine, the drug controlled blood glucose levels during fasting. Exendin-(9-39) also controlled insulin secretion in cell studies of beta cells taken from newborns with HI.

Also, De León-Crutchlow and HI Center researcher Katherine Lord, MD, are studying how many children with surgically treated hyperinsulinism develop diabetes and developmental or behavioral problems. From this study, researchers hope to better understand the long-term risks associated with hyperinsulinism and its treatments and provide better guidance to families.

The center is enrolling subjects who had a pancreatectomy for HI between 1960 and 2008. Subjects will be asked to do an interview with researchers about their blood sugars and medical history and also to complete two developmental/behavioral screens. The interview can be done over the telephone, and the screens will be mailed to subjects. Some subjects can also undergo free diabetes screening and formal neurodevelopmental testing, if they are willing and meet certain criteria. Please call Dr. Lord at 267-425-2125 or email her at lordk@email.chop.edu.