The European research project CureCN aims to develop a curative gene therapy against the ultra-rare Crigler-Najjar syndrome (CN). Crigler-Najjar is a life-threatening liver disease which affects one in a million individuals at birth. The goal of the CureCN consortium is thus to prove the safety and efficacy of an adeno-associated virus (AVV) gene therapy in a clinical trial and make it available to patients.
The inherited Crigler-Najjar syndrome occurs directly after birth. It is caused by the deficiency of a liver-specific enzyme (uridine diphosphate Glucuronosyltransferase 1A1) that leads to the accumulation of toxic unconjugated bilirubin in all body tissues. Untreated, CN causes irreversible neurological damage in the brain and leads to death. The only curative treatment currently available is a liver transplant that implies high risks of complications.
Treatment with phototherapy – a treatment with blue light – reduces symptoms, but is very debilitating as it requires 10 to 14 hours therapy per day. Furthermore, it loses its efficiency over time so that all patients depend upon a liver transplant in the long term. On the other hand, phototherapy does not eliminate the risk of life-threatening spikes of bilirubin. The lack of a permanent curative treatment of CN results in a shortened life expectancy of the affected patients.
Main Goals within CureCN
Partners in CureCN have been chosen for their complementary scientific excellence, technical expertise, and experience in translational research. Joining forces, they take on the mission to find a curative treatment for CN syndrome. The project’s major goals are:
- Developing a curative AAV gene therapy and validating a technology transposable to many other inherited liver-related disorders
- Proving the safety and efficacy of the vector-mediated gene transfer with AAV in a clinical trial
- Providing a treatment suitable for very young CN patients as well as for older patients with a pre-existing immunity to AAV
- Verifying a way to eradicate pre-existing immunity to AAV
- Accelerating the orphan drug development towards a marketing authorisation for the treatment
Another important goal is to establish the first global Crigler-Najjar patient registry. Overall, CureCN wants to provide better information for patients, families, healthcare providers and the general public about CN syndrome and existing treatments.