Refining combination brain and eye gene therapy in a model of CLN5 Batten disease

Dr Samantha Murray, Lincoln University

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) is a group of fatal lysosomal storage disorders that mostly affect children. Collectively, NCLs represent one of the most common inherited neurodegenerative diseases in childhood, with a worldwide incidence of 1 in 12,500 live births.

A relatively rare but devastating disease in New Zealand

In New Zealand, around four children are diagnosed with Batten disease each year. Symptoms progress rapidly, causing deafness, blindness and paralysis, often before children reach their teenage years. The average life expectancy ranges from 8 to 20 years. Batten disease also imposes a substantial financial burden on families. A patient requires 24/7 care at a cost of $60,000-$100,000 a year, according to Lysosomal Diseases New Zealand.

Gene therapy may provide a much needed cure

There is no cure for Batten disease and few treatments available to slow or halt its progression. However, gene therapy trials in naturally-occurring sheep models of CLN5 and CLN6 Batten disease look encouraging. Recombinant adeno-associated viruses (AAV) are engineered to carry a correct copy of the defective NCL gene into affected cells. This allows production of a functional protein to either stabilise or reverse a clinical disease state (Mitchell et al., 2018).

Dr Murray’s team has trialled a combined brain and eye therapy in sheep

Dr Murray and her team recently completed trials of combined brain and eye gene therapy in CLN5-affected sheep. They were able to protect the sheep’s brain and eyes from disease-related dysfunction and degeneration. The promising results have led to the preparation of an ‘Investigation New Drug’ application to the U.S. Food and Drug Administration for human trials.

Cure Kids is funding research to support proposed human trials

With the help of funding from Cure Kids, Dr Murray’s team are continuing their work on combination brain and eye-directed CLN5 gene therapy in sheep. This important project will be timed to fit in with a proposed clinical trial in humans being run by Neurogene Inc.