A study has highlighted the safety of gene-therapy vector GNT0003 in managing Crigler-Najjar syndrome, clarifying they have reported no serious adverse events in patients treated with it. They mentioned that Those receiving higher doses had decreased bilirubin levels and were not receiving phototherapy for at least 78 weeks after vector administration.
This study, “Gene Therapy in Patients with the Crigler–Najjar Syndrome”, by Dr Lorenzo D’Antiga, M.D. and colleagues is published in the New England Journal of Medicine.

Highlighting study background, researchers said due to the absence of enzyme uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) in Crigler–Najjar syndrome patients, there occurs severe unconjugated hyperbilirubinemia causing irreversible neurologic injury and death. Prolonged, daily phototherapy controls jaundice partially, but liver transplantation remains the only definitive cure.
In the present study, researchers reported the safety and efficacy of a single intravenous infusion of an adeno-associated virus serotype eight vector encoding UGT1A1 in patients being treated with phototherapy. The efficacy researchers defined a serum bilirubin level of 300 μmol per litre or lower measured at 17 weeks, one week after phototherapy discontinuation.
Five patients received a single infusion of the gene construct, GNT0003.
The summary of this study includes:
Two patients received 2×1012 vector genomes (vg) per kilogram of body weight.
Three patients received 5×1012 vg per kilogram.
The primary endpoints were measures of safety and efficacy.
They reported common adverse events such as headaches and altered levels of liver enzymes, there was no evidence of serious adverse events.
In four patients, Alanine aminotransferase increased to levels above the upper limit of the normal range, a finding potentially related to an immune response against the infused vector. A course of glucocorticoids treated these patients.
By week 16, patients receiving a lower dose of GNT0003 had serum bilirubin levels exceeding 300 μmol per litre.
Those receiving the higher dose reported having bilirubin levels below 300 μmol per litre in the absence of phototherapy at the end of follow-up.
They said we have not reported any serious adverse events in Crigler–Najjar syndrome patients during their treatment journey with gene-therapy vector GNT0003.
The noted patients receiving higher doses of therapy had a decrease in bilirubin levels.
Genethon funded the study.
Further reading:
https://www.nejm.org/doi/full/10.1056/NEJMoa2214084