Crigler-Najjar’s disease is a rare genetic genetic disease due to the deficiency of a specific enzyme. This deficit leads to a concentration in the blood of bilirubin (chronic jaundice) which can become toxic to the brain. Only phototherapy makes it possible to reduce the level of bilirubin, forcing the patients to stay under blue UV lamps until 12 hours per day.
Fanny Collaud, researcher in the team “Immunology and gene diseases of the liver” of Généthon, explains Crigler-Najjar’s syndrome:
A trial of gene therapy in progress
Developed by Généthonthe AFM-Telethon laboratory, within the “Immunology and Liver Diseases” team led by Dr. Giuseppe Ronzitti, the current gene therapy test aims to correct the genetic anomaly responsible for Crigler-Najjar. It consists of Bring a functional copy of the defective gene directly into the liver cells to restore its ability to eliminate bilirubina toxic pigment that accumulates in the blood of patients with the disease.
Since 2017, an international clinical trial, of which Généthon has been the promoter, has been underway in France (Béclère hospital in Clamart), Italy (two centers) and the Netherlands. Some patients were treated and the first results of this drug candidate are promising: the treatment has proven to be safe, well tolerated, and some of them were able to interrupt phototherapy. The trial of this innovative treatment continues with the inclusion of new patients and long -term monitoring of patients already treated to assess the persistence of efficiency.
Live with or without lamp: two courses, the same fight
Elena, 14, joined the pivot phase of the gene therapy test in 2023. Diagnosed shortly after birth, she spent almost 13 years under her phototherapy lamps at night. But, since July 2023, his life and that of his family has changed! She benefited from the treatment developed by Généthon and 4 months after the injection, Elena was able to stop her phototherapy. Today, the teenager is enjoying a new life :
Elena’s story testifies to the concrete benefits of this therapeutic advance. But it recalls to date, all patients cannot benefit from it. Like Kelly17, who Always live under phototherapy, between 10 and 12 hours a day.In question: the presence of anti-AV antibodiesdeveloped when their immune system has already been exposed to the virus used as a vector to transport the therapeutic gene. These antibodies prevent the viral vector from effectively reaching the livermaking the treatment ineffective.
To overcome this immune lock, Généthon currently conducts the IDES test. This one assesses the interest of a Pre-processing by Imlifidasean enzyme capable of temporarily eliminating anti-AV antibodies before the administration of the viral vector. This innovative protocol could allow patients so far excluded to access gene therapywhile opening the way to new indications in other rare diseases confronted with the same obstacles.
A disease at the heart of AFM-Téléthon’s commitment
The advances carried by genethon in Crigler-Najjar illustrate the capacity of gene therapy to transform the life of the patients. But they also recall that Research must continue to respond to all situationsincluding those of patients today excluded from treatments.
Through its Généthon laboratory and all of its actions, AFM-Téléthon pursues a clear objective: bring out innovative therapies for rare diseases, 95% of which are still without therapeutic solution. Today, the association supports 40 clinical trials in 33 pathologies Touching muscle, skin, blood, brain or vision.
