Crigler-Najjar syndrome is a rare autosomal recessive disorder caused by mutations in the UGT1A1 gene, which result in the toxic accumulation of bilirubin, a substance made by the liver in the body. Indeed, when the UDP-glucuronosyltransferase 1 isotype A1 (UGT1A1), the enzyme responsible for removing bilirubin, doesn't work, the substance accumulates, causing a severe and chronic jaundice, and becoming toxic for the brain and leading to lethality.
Gene therapy has allowed the restoration of an equivalent level of bilirubin to those found in healthy animals Federico Mingozzi team (Généthon, Evry/France), in collaboration with the team of Andres Muro (ICGRB, Trieste/Italy) and the team of Piter Bosma (AMC, Amsterdam/Netherlands), transferred with an AAV vector (adeno-associated virus), developed by Généthon, a copy of the UGT1A1 gene (coding for the production of the UGT1A1 enzyme) in liver cells (hepatocytes) of rats and mice carriers of the anomaly. After injection, levels of bilirubin in the treated animals became equivalent to those of healthy animals. The correction was confirmed more than 6 months after gene therapy, without requiring prior immunosuppression or additional intervention. The researchers demonstrated that a single injection of the AAV vector-UGT1A1 enabled the long-term correction of the Crigler-Najjar syndrome in the treated animals.
Towards a phase I/II clinical trial
The Crigler-Najjar syndrome
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