A new study published in the journal Gastroenterology, revealed that bile ducts malformation could cause serious liver disease in children with Alagille Syndrome. Using a mouse model the researchers found a new biomarker for bile duct malformation that could provide a way for development of new therapy.
Alagille Syndrome is a rare genetic disorder; globally it affects about 2 in 100,000 children. Some of them become very ill with chronic liver and heart problems, sometimes with serious cases that require a transplant. The symptoms includes, itching, deformities of the eyes or bones due to the mutation in JAGGED1 gene. Even it can affect kidney health, and can cause growth disorders in children.
The researchers at Karolinska Institute in Sweden discovered with the aid of a new mouse model that mutation of JAGGED1 gene could cause the deformity in certain cell types as well as in bile ducts of liver. The substitution of a specific amino acid coded for Notch ligand in JAGGED1, interrupt the Notch ligand and the Notch 1 receptors interaction, the researchers found.
“The discovery is important and opens up possibilities for new, more specific treatments," says Emma Andersson, assistant professor at Karolinska Institute’s Department of Biosciences and Nutrition. "We hope to be able to use our mouse model to understand the disease better, predict which children will need a transplant and ultimately find a cure."
Additionally the researchers received liver biopsy from patients and studied it using RNA sequencing. "The liver samples were the most important piece of the puzzle for our study," says Dr Andersson.
The comparison of mouse model and liver biopsy results shows that the study findings are relevant to human. Additionally the researchers could find a new biomarker for malformation of bile duct in patient with Alagille Syndrome, which would pave the way for identification of new and more effective treatment.