\ Innovazione \ ICGEB Team instrumental in proving efficacy of gene therapy in metabolic liver disease

ICGEB Group Leader, Mouse Molecular Genetics Lab, Dr. Andrés F. Muro and Research Associate, Dr. Giulia Bortolussi have taken part in the European research project CureCN, which aims to develop a curative gene therapy for the ultra-rare Crigler-Najjar syndrome (CN) – a life-threatening liver disease which affects one in a million individuals at birth.

The project commenced in 2013 and is led by Généthon, France and sponsored by the European Commission programme H2020. The consortium includes 11 partners from six European countries and has involved the external collaboration of ICGEB which was pivotal in generating pre-clinical data using its Ugt1a KO mouse model, thus setting the basis for the subsequent clinical translation of the trial.

The results of the trial were published on 17 August in a joint manuscript in the New England Journal of Medicine, co-authored by Dr. Bortolussi and Dr. Muro. These represent the first clinical demonstration of the efficacy of gene therapy in a metabolic disease of the liver, demonstrating the safety and tolerance for the treatment as well as its efficacy at the highest dose.

The trial demonstrated restored long-term expression of the missing enzyme with a large reduction in plasma bilirubin levels in the three adult patients treated with the highest dose. The current part of the study, launched in January 2023, aims to confirm the observed effect in a larger number of patients including children aged 10 years and over, the age at which the liver matures. Should the results be conclusive, this would enable a product license application at the French and European authorities.

Dr. Muro states: “We are very proud of our contribution to the trial. The obtained in-patient results represent a fundamental step forward towards the application of gene therapy non only for Crigler-Najjar patients, but also for other liver genetic diseases. This is the first report of a long-term correction of a disease caused by a non-secreted liver protein.”