INTRODUCTION

1. CLN5,6&? BDSRA 2012 INTRODUCTION Large animal models for Batten disease enable research towards a better understanding of the disease mechanisms and are important for the evaluation of therapeutic approaches in preclinical trials. Over the last decade researchers in Australia (1) and New Zealand have been working on Batten disease, using flocks of sheep (2) to study aspects of the human diseases, and we have integrated our activities through the formation of the Batten Animal Research Network (BARN). • PAST RESEARCH HIGHLIGHTS • Establishment of the NCL Merino research flock • Identification of the mutations causing the CLN6 form in South Hampshire sheep and a different CLN6 form in Australian Merinos • Identification of the mutations causing CLN5 in Devon cattle What this means For Therapy • The identification of the disease causing genes and mutations in these animal models allows preclinical diagnosis from conception and us to match an animal model to the corresponding human NCL • Therapeutic approaches (e.g. pharmaceuticals, gene and stem cell therapies) need to be evaluated for safety and efficiency. The use of both small and large animal models is recommended before clinical trials in humans commence. • To assess the efficiency of therapeutic approaches in animals we need to have a range of measures of disease progression over time – MRI and behavior measures appear to be useful in this context. • Current Projects • Molecular characterisation of NCL in horses. • B) Development of non-invasive methods to determine pre-clinical pathology in Merino sheep, to allow monitoring of the efficacy of treatments under trial (3-5). 3 4 1 1. The Australian BARN team: Imke (left) and past and current PhD students Peter (middle) and Izmira (right) Animal Models: Sheep, cattle and horses with NCL Imke Tammen, Peter J. Houweling & Izmira F. Mohd Ismail, Faculty of Veterinary Science, The University of Sydney, Australia (imke.tammen@sydney.edu.au) and Batten Animal Research Network (BARN) 5 2 3-5. Magnetic resonance imaging (3) and behavioural studies (4&5) in Australian Merino sheep with NCL for the development of longitudinal in vivo markers for disease progression. Acknowledgements: Technical support by D. Palmer and G. Attard as well as the support of honours students (D. Beganovic, N. Foreman, B. Lui, H. Okazaki, A. Sutton & E. Wan) and colleagues (G. Cronin, A. Hollmann, K. Hughes, E. Jonas, M. Makara, P. Thomson, C. Wade, C. Willet & S. Zaki) is acknowledged. 2. The Australian NCL Merino research flock