Généthon gene therapy GNT0003: effect persists four years in three Crigler–Najjar patients
A follow-up in the New England Journal of Medicine reports that the benefit of AAV8 gene therapy persisted four years after dosing in three patients with a rare liver disorder.
On November 5, 2026, the New England Journal of Medicine published a four-year follow-up of GNT0003, an AAV8-mediated gene therapy for Crigler–Najjar syndrome, according to miragenews.com. miragenews.com
miragenews.commiragenews.comOpen source ↗ The clinical trial was sponsored by Généthon, a non-profit gene therapy organization founded by the French Muscular Dystrophy Association (AFM-Téléthon), as part of the international CureCN consortium.
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Disease and approach
Crigler–Najjar syndrome is an extremely rare congenital liver disorder affecting approximately 500 people in Europe. It is caused by a deficiency of the enzyme UGT1A1, which is required for bilirubin metabolism. Accumulated bilirubin can lead to irreversible neurological damage and, in the most severe cases, death. miragenews.com
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Patients currently control bilirubin levels with blue-light phototherapy. Liver transplantation is the only definitive curative option, but it carries a risk of complications. GNT0003 aims to restore UGT1A1 expression in the liver and correct bilirubin levels. miragenews.com
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Four-year results
Lorenzo D'Antiga of Papa Giovanni XXIII Hospital in Bergamo, Italy, and co-authors documented that the effect persisted in the three patients who received the therapeutic dose at the hospital. Two of them were able to stop phototherapy; the third kept a partial response and requires less phototherapy exposure. In all three, bilirubin remained significantly below the threshold associated with the risk of neurotoxicity. miragenews.com
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The investigators also observed sustained normalization of alanine aminotransferase (ALT), a key marker of liver health and function, in the three patients treated at the highest dose. According to the report, this had never been achieved with phototherapy alone. One patient completed a pregnancy without complications after gene therapy and gave birth to a healthy baby. miragenews.com
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The publication follows the results of the phase 1–2 CureCN trial, published in the New England Journal of Medicine in 2023. Those results showed the safety of the treatment and its ability to correct the disease, allowing patients who received the therapeutic dose to stop phototherapy. miragenews.com
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The pivotal part of the trial, which began in January 2023, aims to confirm the observed effect in a larger patient population, including children aged 10 years and older, the age at which the liver reaches maturity. miragenews.com
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D'Antiga, the principal investigator, noted that AAV vector gene therapy had so far shown clinical efficacy in hemophilia A and B, and that there is now also a clear signal of efficacy in Crigler–Najjar syndrome. Giuseppe Ronzitti of Généthon said the four-year results confirm the potential of GNT0003 for sustained efficacy over time.
