Gene therapy has proved to be a promising treatment against metabolic liver disease in animal trials. Pigs transplanted with gene-corrected liver cells avoided many complications associated with the illness.
Today, patients who suffer from inherited metabolic liver disease have little option other than liver transplantation as they often become resistant to current treatments.
The latest study, published in the journal Science Translational Medicine, tried a novel approach to treat liver disease. It is based on the use of transplanted gene-corrected cells which work by regenerating the liver.
Prevention of liver failure
The researchers specifically worked on hereditary tyrosinemia type I (HT1), a rare liver disease caused by a genetic defect in FAH, a key metabolic enzyme. Patients with HT1 are particularly vulnerable to developing treatment resistance, so finding options for them is crucial.
The team designed and tested an ex vivo gene therapy approach in FAH-deficient pigs. The principles behind this method are simple: the scientists removed liver tissue from the animals and delivered the missing FAH gene into these cells using a lentiviral vector – a subclass of virus with an ability to integrate the genome of non-dividing cells.
The correcte cells were then transplanted back into the pigs, less than 24 hours after being collected. The experiment appeared to be successful. Indeed, the gene-corrected cells expanded and repopulated the entire liver, thus improving metabolic liver function significantly. The intervention prevented liver failure and fibrosis or scarring in pigs for up to a year, emphasising the great potential of this method.
Ex vivo gene therapy may offer a new, concrete strategy for curing metabolic liver disorders.