CN-I LIVER THERAPYProject reference: 625689
Funded under :
POTENTIAL OF INDUCED PLURIPOTENT STEM CELLS FOR THE TREATMENT OF CRIGLER-NAJJAR LIVER DISEASE: A PRECLINICAL SAFETY ASSESSMENT
Total cost:EUR 199 317,6
EU contribution:EUR 199 317,6
Topic(s):FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development"
Call for proposal:FP7-PEOPLE-2013-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
"Currently, the only cure for many inherited metabolic liver diseases with severe extra-hepatic manifestations, such as Crigler-Najjar disease (CNI), is liver transplantation (LT). LT goes together with heavy surgery, life-long immunosuppression and important public health costs. Development of less invasive treatments will permit important benefits for the patients and economic savings. Combination of gene therapy and hepatocyte (HEP) transplantation is a promising alternative to LT, correcting the metabolic defect while keeping in place the normal native liver. Nevertheless, the major obstacle has been shown to be the insufficient amount of corrected HEP available for transplantation. Induced pluripotent stem cells (iPS) are endowed with intrinsic self-renewal ability and the potential to differentiate into any of the three germ layers allowing cell amplification before differentiation. As such, iPS are heralded as the most promising avenue for cell-based therapeutics. However, recent evidences indicate that the epigenetic features of iPS are heterogeneous and notably influenced by the tissue of origin of the reprogrammed cells.
Hypothesis: HEP reprogramming and differentiation induce profound epigenetic changes that could affect the safety of gene and stem cell therapy combination approach.
Objectives: 1) Reprogramming of patient-specific CNI-HEP into iPS. 2) Correction of CNI-iPS by ex vivo lentiviral transduction. 3) Large-scale amplification of the corrected CNI-iPS and differentiation to HEP-like cells. 4) Epigenetic analysis of patient CNI-HEP, CN-iPS and the differentiated-corrected cells. 5) Therapeutic assessment of corrected CN-HEP-like cells into the liver of the CNI animal model.
This project will allow a step forward to studying the safety, efficacy and clinical potential of differentiated cells derived from patient-specific iPS. Importantly, not only CNI disease but also many other inborn liver disorders are potentially treatable via this approach."
EU contribution: EUR 199 317,6
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