Combined brain- and eye-directed gene therapy in ovine Batten disease

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases of childhood with a worldwide incidence of 1:12,500 live births. Affected children lose their vision, suffer seizures and experience physical and cognitive decline. There is currently no cure.

Lincoln University has unique flocks of sheep with a naturally occurring CLN5 variant of Batten disease. Clinical and neuropathological disease progression is well defined in these sheep which have proven to be excellent models of the human condition. Corrective gene therapy delivered to the brains of CLN5 affected sheep showed exciting results, protecting against stereotypical brain atrophy and clinical decline, as monitored by in vivo non-invasive methods and verified post mortem. 

We are in the final stage of bringing this therapy into human clinical trials. However treated sheep still went blind, but recent findings from a pilot study of ocular gene therapy were encouraging. Gene therapy to one eye of affected sheep provided long term protection from loss of retinal cell activity compared to the untreated eye.

We plan to trial combined brain- and eye-directed gene therapy in both pre- and post-symptomatic CLN5 sheep in an effort to prevent both neurological disease and retinal degeneration simultaneously.