First clinical trial results showing sustained efficacy of gene therapy for patients with Crigler-Najjar syndrome were published in the New England Journal of Medicine. A single dose lowered bilirubin below the toxic threshold. Only the administration of the maximum dose allowed the interruption of phototherapy for at least 18 months.
Crigler-Najjar syndrome is a rare and hereditary metabolic liver disease with autosomal recessive transmission. In these patients, the activity of the enzyme UGT1A1 (UDP-glucuronosyltransferase 1-1) is reduced or absent. The enzyme is involved in the glucuronidation of unconjugated bilirubin in the liver. Thus, the clinical picture is the consequence of the increase in the level of unconjugated bilirubin in the blood.
In the absence of prompt therapeutic interventions, hyperbilirubinemia can cause severe, including fatal, neurological damage. Currently, the only therapeutic options are phototherapy for 12 hours a day or liver transplantation.
GNT0003 gene therapy for Crigler-Najjar syndrome, developed by Genethon, uses an AAV8 (adeno-associated virus serotype 8) vector, which contains a copy of the UGT1A1 gene. The new results demonstrate that this method enables gene expression for the UGT1A1 enzyme to be obtained.
The clinical study debuted in 2017, including four centers in France, Italy and the Netherlands. Gene therapy was administered to a group of 5 women aged 21 to 30. The phase I/II clinical trial confirmed the safety and tolerability of the gene therapy, with no serious adverse reactions reported. There have been cases of liver enzyme changes and headaches, which could be treated and resolved.
The next stages of the study involve enrolling a larger number of patients with Crigler-Najjar syndrome, including children at least 10 years old. The target of the phase I/II clinical trial is the investigation of gene therapy GNT0003 in 17 patients with severe forms of Crigler-Najjar syndrome.
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2023-10-24 08:21:33
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