Crigler-Najjar Syndrome is a rare genetic liver disease leading to irreversible neurological complications due to the neurotoxicity of unconjugated bilirubin. Symptomatic treatment of the disease involves 10-12 hours of phototherapy every day (up to 18 hours during infectious episodes), performed while the patient is sleeping.
Today, the only possible cure is liver transplantation, the disadvantages of which remain major (operating risks, graft lifespan, intolerance to anti-rejection treatments.
The team of Dr. Federico Mingozzi at Genethon, in collaboration with Dr. Philippe Labrune (AP-HP, Antoine Béclère Hospital, Clamart, France), Dr. Piter Bosma (Academic Medical Center, Tytgat Institute, Amsterdam, The Netherlands), and Dr. Andres Muro (International Center for Genetic Engineering and Biotechnology, Trieste, Italy), has developed a gene therapy treatment to restor bilirubin-glucuronosyltransferase activity in the liver of patients.
After the period of recruitment and prior observation of patients, Professor Labrune at the Beclère Hospital in Clamart injected the first patient in early December 2018 in France.
Genethon is promotor of this phase I / II trial, an intravenous injection of an AAV vector that transfers a copy of the UGT1A1 gene (coding for the production of bilirubin GT) into liver cells. Over the next few months, 17 patients will be treated.
The European CareCN trial will assess the tolerance of the product, define the optimal dose and evaluate the therapeutic efficacy of the drug candidate. It takes place in 4 research centers in Europe: in France (Pr Labrune, Béclère Hospital in Clamart); in Italy (Pr Brunetti-Pierri, Federico II Hospital in Naples and Pr d’Antiga, Azienda Ospedaliera Papa Giovanni XXIII in Bergamo) and in the Netherlands (Pr Beuers, Academic Medical Center in Amsterdam).