Progressive Familial Intrahepatic Cholestasis

Progressive familial intrahepatic cholestasis is a rare genetic disorder that causes progressive liver disease, which typically leads to liver failure. Progressive Familial Intrahepatic Cholestasis is inherited in an autosomal recessive way, meaning that there are mutations in both copies of the gene in order for the disease to be present. The disease is estimated to affect one in every 50,000 to 100,000 people worldwide. In people with Progressive Familial Intrahepatic Cholestasis, liver cells are less able to secrete bile due to mutations in proteins that control bile homeostasis. The resulting buildup of bile in liver cells causes liver disease in affected individuals.Three types of Progressive Familial Intrahepatic Cholestasis have been identified.

In all cases the main clinical presentation includes cholestasis, pruritus and jaundice. PFIC1, also referred to as Byler disease, is caused by impaired bile salt secretion due to mutations that effect the FIC1 protein. PFIC2 is also caused by impaired bile salt secretion due to a different mutation that encodes the bile salt export pump protein (BSEP). Both usually present in the first months of life with features of neonatal cholestasis.

PFIC3, which may also occur in infancy or later in childhood or even during young adulthood, is a result of impaired multi-drug resistant 3 protein (MDR3).Serum bilirubin is not necessarily increased in Progressive Familial Intrahepatic Cholestasis, but elevation of serum bile acids is a nearly uniform feature of the disease. The most prominent and problematic on-going manifestation of Progressive Familial Intrahepatic Cholestasis is pruritus. In the absence of treatment, progressive liver disease occurs in nearly all patients.

Inhibiting the ASBT, which is responsible for recycling bile acids back to the liver, may mimic the effects of successful surgical approaches that reduce bile accumulation in the liver, thereby improving liver function and symptoms of disease.

Lumena is planning to conduct a Phase II clinical study of LUM001 in children with Progressive Familial Intrahepatic Cholestasis. | More Information »