Developing a new gene therapy for children with a rare severe liver disease

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare severe inherited disorders that mostly affect young children and cause progressive liver disease. A liver transplant is the only curative treatment for children with PFIC, but this is a major operation and has a risk of complications – and there is a shortage of donor livers. Professor Paul Gissen of the UCL Great Ormond Street Institute of Child Health is carrying out laboratory research to develop a new gene therapy for children with PFIC type 3 (PFIC3). If successful, this could ultimately lead to a safer and better treatment option for children with this life-threatening condition.

How are children’s lives affected now?

PFIC3 is caused by faults in a gene called ABCB4, which provides the instructions to make a protein needed for healthy liver function.

“A child with PFIC3 will experience severe itching, yellowing of the skin and whites of the eyes – and slower than expected growth,” says Professor Gissen. “These symptoms will usually start in the first year of life and get worse over time, leading to complete liver failure later in childhood or early adulthood.”

In children with PFIC3, the bile – a digestive fluid produced by the liver – lacks an essential component that protects the cells lining the bile ducts (the tubes along which the bile flows from the liver) from the corrosive properties of bile. Eventually, these damaged cells stop working and the liver fails.

“A liver transplant is the only curative treatment for PFIC3 – but this is a major operation and the need for new livers far outweighs the number of donors,” says Professor Gissen. “There is an urgent need for alternative treatment options for children with this serious condition.”

How could this research help?

The researchers plan to use a harmless virus to deliver a working copy of the ABCB4 gene into liver cells. This type of gene therapy has successfully been used to treat other genetic diseases and shown to be safe.

“We will test our new gene therapy in the laboratory to find out if it is a safe and effective way of treating liver disease,” says Professor Gissen.

If this treatment shows promise, it could be a stepping stone toward setting up a clinical trial for children with PFIC3.

“If successful, this innovative gene therapy could help to transform the lives of children with PFIC3 – sparing them from the long waits and complications often associated with liver transplants,” says Professor Gissen.

We do not provide medical advice. If you would like more information about a condition or would like to talk to someone about your health, contact NHS Choices or speak to your GP.