The preliminary results of a clinical trial for Crigler-Najjar syndrome, a rare liver disease, were presented at the EASL (European Association for the Study of the Liver) congress on June 26, 2021. With firsts encouraging observations.
A rare genetic disease of the liver, Crigler-Najjar syndrome is characterized by the abnormal accumulation of bilirubin in the body. This excess of bilirubin is due to the malfunction of an enzyme (UGT1A1) responsible for transforming bilirubin into a substance that can be eliminated by the body.
However, when bilirubin accumulates, it causes intense and chronic jaundice and becomes toxic to the brain, which can cause severe neurological damage and become fatal.
Fanny Collaud, researcher at Généthon, tells you more about this ultra rare syndrome:
At present, only phototherapy can reduce the bilirubin level, forcing patients to stay under blue lamps for up to 12 hours a day.
A gene therapy trial, with a drug candidate developed by the “Immunology and Genetic Therapy of Liver Diseases” team, led by Dr Giuseppe Ronzitti at Généthon, has started in France, Italy and the Netherlands . This European trial, sponsored by Généthon, the AFM-Telethon laboratory, aims to ensure the tolerance of the product, define the optimal dose and assess the therapeutic efficacy of the drug candidate.
“ The team worked a lot on this project from conception and development of the approach to testing. In fact, we designed the drug candidate, demonstrated its preclinical efficacy, and then designed the product for the clinical trial. »Explains Dr Giuseppe Ronzitti.
Gene therapy involves providing liver cells with a copy of the gene (UGT1A1) encoding an enzyme that eliminates bilirubin.
The preliminary results have just been presented at the International Liver Congress by Dr d’Antiga, one of the trial investigators (Bergamo, Italy). According to the first observations, the drug candidate is well tolerated and shows the first therapeutic effects which remain to be confirmed during the continuation of the trial.
Indeed, the first two cohorts demonstrate the safety and good tolerance of the product in the 4 patients treated, as well as a dose effect to be confirmed.
In cohort 1, treated at the lowest dose, clinicians observed a transient therapeutic effect but did not allow prolonged stopping of phototherapy at the 16th week post-injection (product efficacy criterion)
In cohort 2, treated at a higher dose, the first patient shows a strong decrease in the bilirubin level which allowed her to stop phototherapy for several weeks. The second patient also saw her bilirubin level drop sharply. Her treatment is too recent to demonstrate a stable drop in this rate, but if this drop is confirmed, this patient will in turn be able to discontinue phototherapy within a few weeks.
“ These first observations presented at the last EASL congress show that gene therapy could become a therapeutic alternative for this severe liver disease. We must remain cautious because the trial is continuing and will allow us to evaluate these encouraging first results over time and in other patients. »Declares Frédéric Revah, General Manager of Généthon.
Provided by AFM-Telethon