A collaborative research team from Baylor College of Medicine, UMass Chan Medical School, and Cincinnati Children’s Hospital Medical Center has announced a potential breakthrough in the treatment of Alagille syndrome. This genetic condition affects multiple organs, most notably the liver, where it can lead to failure. The study, published in Gastroenterology, reveals that gene therapy could improve liver health and bile duct development in mouse models.
Dr. Hamed Jafar-Nejad, a professor at Baylor and corresponding author of the study, explained the condition: “Alagille syndrome is a genetic disease that affects about 1 in 30,000 individuals. The hallmark of the condition is a significant decrease in the number of ducts that transport the bile out of the liver.” He further noted that current treatments only aim to delay disease progression.
The research focused on the Sox4 gene. It was initially believed that silencing this gene would worsen symptoms; however, researchers found that reducing Sox4 levels actually improved bile duct formation in mice with Alagille syndrome. Duncan Fox, a graduate student involved in the study, stated: “We used adeno-associated viral gene therapy to deliver a small RNA molecule that silences the Sox4 gene specifically in mouse liver cells.”
Fox reported promising results: “One dose of the treatment led to the formation of more functional bile ducts, reduced liver scarring and inflammation, and improved overall liver structure and function into adulthood.” Importantly, these improvements were observed even when administered after signs of liver damage had appeared.
The study signifies progress toward finding a cure for Alagille syndrome. Dr. Jafar-Nejad expressed optimism: “We are excited that our research points out the possibility that a single gene therapy injection could restore biliary system and liver function... This suggests... patients with Alagille syndrome might avoid the need for a transplant.”
The research team includes contributors Jun Xie, Jennifer L. Burwinkel, Josh M. Adams among others from affiliated institutions. Funding was provided by various sources including Baylor College of Medicine's Department of Molecular and Human Genetics and several National Institutes of Health grants.
Further studies are planned to ensure safety and understand how this therapy works at a molecular level before proceeding to clinical trials.
