Researchers focus on causes of biliary atresia, a potentially fatal illness in infants

Dr. Rebecca G. Wells

For parents whose newborn babies are diagnosed with biliary atresia (BA), it can mean surgery and even a need for a liver transplant. There is no cure for this potentially fatal illness. But with their BSF-funded project, Dr. Rebecca G. Wells of the Perelman School of Medicine at the University of Pennsylvania, and Dr. Orith Waisbourd-Zinman, from the Schneider Children’s Medical Center in Israel, hope to make inroads that lead to new treatments. For their efforts, they are the winners of BSF’s Neufeld Memorial Award.

Named in memory of Prof. Henry Neufeld, who was instrumental in BSF’s growth and chaired the Board of Governors three times, the award is given annually to new BSF grantees who have the most outstanding and original new project in the health services field. The honor includes a $10,000 grant, presented in addition to the original BSF grant.

BA begins in seemingly healthy newborns as obstruction of the bile ducts, which normally connect the liver to the gut and allow bile to flow from the liver to the intestine. Because infants with BA are unable to excrete bile from the liver, bile backs up in the liver and causes liver damage, such that babies become jaundiced and develop liver injury, followed by liver scarring and end-stage liver disease.

The cause of this disease remains unknown, but recent data suggests that the mother is exposed to a virus or toxin during pregnancy. This causes the baby to be born with mild, asymptomatic bile duct damage, and then the injury and damage progress in the first few months of life.

Dr. Orith Waisbourd-Zinman

Wells and Waisbourd-Zinman have already isolated a novel toxin called biliatresone from Australian plants that, when eaten by pregnant livestock, caused BA in newborns (but left mothers healthy).

“We found that biliatresone causes BA in zebrafish and is therefore likely the cause of the disease in livestock,” said Waisbourd-Zinman. “We are using this toxin to help understand mechanisms of BA in humans.”

The team has also studied the effect of biliatresone on bile duct cells and biliary trees isolated from mice. Biliary trees refer to the liver, gall bladder and bile ducts, and how they work together to make, store and secrete bile. Their preliminary data shows that biliatresone causes cell stress, damage to the cell skeleton, changes in cell orientation, increased leaking of the bile ducts, and ultimately formation of scar tissue surrounding the bile ducts.

As part of their current project, Wells and Waisbourd-Zinman hope to determine what initially causes injury to newborn bile ducts, to understand why this injury progresses, and to test new therapies based on the information they discover.

“We believe that if we gain further understanding of the potential mechanisms of initial injury in BA, this could lead to transformative new treatments,” Wells said.