Development of Exendin-(9-39) for the Treatment of Congenital Hyperinsulinism

National Center For Advancing Translational Sciences

Investigators

Abstract

Congenital hyperinsulinism is a rare, inherited disease affecting about 1:25,000 to 1:50,000 infants. In this disorder, the beta cells (cells that produce insulin) in the pancreas produce too much insulin and at the wrong time, leading to low blood sugar. Four types of congenital hyperinsulinism are known, caused by different genetic mutations. The disease can be difficult to identify in babies because the symptoms include irritability, sleepiness, lethargy and excessive hunger, but in severe cases, it can be life threatening, with seizures and coma. Current treatments include feeding more sugar, medication to control insulin secretion and surgery to remove part of the pancreas. These researchers are working on a drug to treat one type of congenital hyperinsulinism that does not respond to any current medication and is typically treated by near-total removal of the infants pancreas. The new drug acts by blocking the activity of a protein called glucagon-like peptide-1 receptor, reducing insulin secretion. The collaboration included the completion of the following studies -Synthesis of Good Manufacturing Practice (GMP) and non-GMP material -Formulation development -Pharmacokinetic/absorption, distribution, metabolism and excretion (PK/ADME) studies -Investigational New Drug (IND)-directed toxicology