Hepatic

Cell culture and mouse studies suggest liver-targeted TGFBR1 gene therapy could help treat Alagille syndrome, a genetic disease that affects the liver, bile duct and other tissues. In a mouse model of Alagille syndrome, TGFBR1 encoded in a liver-tropic adeno-associated viral (AAV) serotype 8 (AAV8) vector promoted the development of a mature biliary network in 9 of 11 mice, whereas none of 9 untreated mice developed a biliary network. Also in the model, the AAV8-encoded TGFBR1 decreased cholestasis and liver fibrosis compared with no treatment. Next steps include identifying additional inducers of cholangiocyte and biliary network development in Alagille syndrome as potential therapeutic targets for the disease.

Eli Lilly and Co. has the TGFBR1 inhibitor galunisertib (LY2157299) in Phase II testing for brain and liver cancers and Phase I/II testing for pancreatic cancer...