Quest Continues to Update Screening Technology, Study More Bile Acid Defects

Published November 2018 | Clinical Liver Disease

In the article titled “The Cincinnati Experience,” a pie chart shows the distribution of six distinct types of neonatal cholestasis and liver disease in infants, older children and adults. All have bile acid metabolism defects that present with varying degrees of pathogenesis and mortality.

For co-authors Kenneth Setchell, PhD, and James Heubi, MD, the article is more than a review of what’s known about six of eight such defects. It’s personal, because they identified five of the six defects described in this study.

The article provides detailed descriptions of the pathogenesis, treatment and prognosis for bile acid synthesis disorders that are directly related to defects in the metabolic pathway in the liver.

Setchell and Heubi describe their decades-long collaboration as an ideal example of translational medicine, spanning observation of the defects in the 1980s, presentation of hypotheses for their causes, and identification of the defects in bile acid metabolism. They invented a treatment involving cholic acid, launched a company to test and manufacture the drug, and ultimately won U.S. Food and Drug Administration approval in 2017 of Cholbam, a lifelong therapy for children and adults with bile acid defects and liver disease.

What’s next? The team is collaborating with Children’s Hospital of Fudan University in Shanghai, China, and has identified many children with these bile acid defects. They also are working to develop updated mass spectrometry-based screening technology that other medical centers can use without relying solely on Setchell’s outdated—but still effective—mass spectrometry equipment.

“Every week, we continue to screen urine samples that are delivered to Cincinnati Children’s from around the world,” Setchell explains. “And long-term, we keep hoping we will eventually identify disorders involving the remaining nine of the 17 known enzymes in the pathway of cholesterol to bile acid synthesis.”