Genethon:
a breakthrough

for a rare liver disease

A pioneer in gene therapies, Genethon demonstrated the efficacy of a gene therapy targeting Crigler-Najjar syndrome, a rare liver disease. This was the first-ever demonstration of efficacy for a gene therapy in a metabolic disorder of the liver. Genethon was the sponsor of the study, the results of which were published 16 August 2023 in the New England Journal of Medicine.

Crigler-Najjar syndrome is characterized by hyperbilirubinemia due to a deficiency in the UGT1A1 enzyme. Left untreated, that accumulation of bilirubin in the blood can cause severe neurological damage and even death. Currently, the only available treatments are phototherapy—sometimes up to 12 hours daily—or liver transplantation. In contrast, the drug candidate conceived by Genethon brings a simple intravenous injection to the table to diminish bilirubin levels to below the threshold of toxicity. The gene therapy does this by restoring UGT1A1 expression in the liver. In the study, three of the patients receiving the highest treatment dose were able to stop phototherapy for 18 months or more.

The confirmatory part of the trial is underway with the objective of verifying the observed effects in a larger number of patients, including children aged ≥10 years, age at which the liver is considered mature. Should those confirmatory results be conclusive, the therapy may be registered with French and European health authorities.