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Genetic Anomalies

Towards human translation of gene-therapy for Batten disease

This project will refine current methods of gene therapy in a sheep model with the aim of expediting the therapy to clinical trials.

Associate Professor Nigel Anderson, Dr Nadia Mitchell & Professor David Palmer
University of Otago, Christchurch

What is the problem and who does it affect?

Batten disease is a rare inherited neurological condition which robs seemingly healthy young children of the ability to walk, talk and feed, invariably leading to premature death between infancy and early adulthood. There is no cure and no current effective treatments.

Two flocks of sheep at Lincoln University, Christchurch, have naturally occurring disease states of different forms of Batten disease. Prof David Palmer is a preeminent researcher in the field, assiduously investigating methods and treatments to give these children a chance at life. He has spent decades studying the pathology of the disease in these sheep, and two years ago he and a team of collaborators had a breakthrough in the CLN5 version of the disease.

They found that their therapy was curative in all 6 sheep which were treated. These promising results spurred Cure Kids to spearhead a campaign to raise funds to take advantage of this outcome. What resulted was two projects aimed at expediting therapy from a sheep model to a clinical model, which will hopefully lead to an effective treatment for the afflicted children and their families.

What is the research hoping to achieve?

This current project aims to enhance the successful gene therapy to the point where it is safe to use in humans.  Gene therapy is a method by which a virus is used to do what it does best, infect other cells with its DNA. In this case, the virus is disarmed, meaning it can do its job with no adverse effects to the animal. A corrected copy of the defective gene is then incorporated into the virus aimed, in principle, to produce the corrected gene product which can also be transported to relevant neighbouring cells. The complexity of the brain means constant refinement is required to make sure the best therapy is available for clinical trials. This includes performing post mortem work on the original treated sheep to see which parts of the brain the therapy was able to reach. This is essential for human translation, as the level of success of the therapy depends on the therapy reaching the necessary parts of the brain.

The ability to refine this therapy in naturally occurring sheep models is invaluable, as it allows the team to test many of the human-like characteristics of Batten disease such as slowed motor development, for which they use the ability for the sheep to navigate a maze. They aim to automate the maze method through the use of GPS-monitoring of the sheep to reduce time and human intervention.

Additional to the above-mentioned research, the team will trial the therapy in post-symptomatic sheep. This is a rescue method which is essential for a condition like Batten disease where children appear outwardly normal, with no knowledge of their disease. A treatment that can treat the disease after onset would be critical for many children and families.