1. FP7-BALANCE WP5 LEAD:EDINBURGH AIM: Safety and efficacy of AMC-HepRG BAL in the porcine model of paracetamol-induced ALF Start date : M12 Edinburgh team: Prof Hayes, Dr Plevris, Dr L Nelson (Hepatology) Dr A Lee, Dr A Hay ( Anaesthetics) Prof E Clutton, Dr T King, Dr M Eddleston ( Vet School/Roslin Institute) 2 post-docs (tba)

2. Objectives To obtain proof of principle of safety and efficacy of HepaRG-BAL in a porcine model of ALF Specific objectives: Task 5.1: To develop a reproducible invasively- monitored model of paracetamol-induced ALF in 35 kg Gottingen minipigs Task 5.2: To assess clinical and biochemical parameters in paracetamol-induced ALF pigs under ICU monitoring and therapy conditions. Task 5.3: To assess efficacy/ safety of HepaRG-BAL in three groups of 7 pigs

3. 21 Pigs will be divided into 3 groups, under 3 different BAL system conditions: Clinical-grade (GMP) BAL Systems will be utilized; - Standard ICU/ Clinical treatment (n=7); - BAL System treatment - WITHOUT HepaRG cells (n=7) - BAL System treatment - WITH HepaRG cells (n=7); *A preliminary phase of 5-7 animals to establish the ALF model will start as soon as feasible. *Total expected number of animals 30 ( 2-3 extra animals as contigency). *Experiments will last up to 48 hours, and any animals surviving at this time-point are euthanised.

4. DELIVERABLES D5.1 Establishment of a reproducible invasively-monitored minipig model of paracetamolinduced ALF and related protocols and monitoring systems; M15 -D5.1.1 Robust reproducible paracetamol-induced ALF Model in 35 kg minipigs; M15 D5.1.2 Protocol of intensive care treatment of ALF pigs; M15 - D5.1.3 Monitoring system of haemodynamics, ICP and blood chemistry; M15 D5.2 Report on variability of survival time of paracetamol induced ALF in mini-pigs; M15 D5.3 Report on efficacy/ safety of HepaRG-BAL in three groups of 7 animals, M24 D5.3.1 Knowledge about the efficacy and safety of the HepaRG BAL as a treatment of ALFin mini-pigs; M21 D5.3.2 Functional Genomics Data Bioinformatics Analysis/ Report Completed; M24 D5.3.3 Data from statistical analysis, report Completed; M24