In vivo monitoring of viral medicated gene injection therapy in ovine Batten disease

Abstract

Batten disease (neuronal ceroid-lipofuscinoses, NCLs) is a group of fatal brain wasting diseases of children affecting approximately 1:12,500 live births worldwide, caused by mutations in at least 13 genes. No treatment has been established so far. Forms associated with mutations in two different genes, CLN5 and CLN6, are being investigated in wellestablished sheep models. Defining features are progressive atrophy of the brain and retina, leading to mental degeneration and blindness. Previous and on-going viral mediated gene injection therapy trials have shown remarkable efficacy. The sheep models provide the capacity to follow individual animals over an extended time period compared to other animal models. Long term ongoing in vivo assessments of brain atrophy and visual impairment are essential to monitor treatment trials and provide data for human translation.