Investigating a novel gene therapy in a form of Batten disease

Using an alternative treatment to combat CLN6 Batten disease in a naturally occurring mouse model.

Dr Stephanie Hughes
University of Otago, Dunedin

What’s 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 around the age of 8-12 years old. There is no cure and no current effective treatments.

Dr Stephanie Hughes was a co-principal investigator on a project which proved curative in a sheep model of CLN5 Batten disease. All six treated sheep lived healthily across their normal life-course, save for one having a delayed onset of vision loss.

The intervention in CLN6 sheep, however, was unsuccessful and this is thought to be due to different proteins associated with each disease.

 

What is the research hoping to achieve?

CLN5 encodes a soluble protein which means it can be expressed in one cell and taken up by neighbouring cells – known as cross-correction. This enables greater spread throughout the brain. The CLN6 encoded protein is what is known as membrane-bound, meaning its ability to permeate necessary areas of the brain are hindered by its very molecular composition. It is hypothesised that this is the reason for the disparate differences between CLN6 and CLN5 in the aforementioned study.

The team will trial a novel form of therapy which they believe can effectively allow CLN6 cross-correction.

The therapy will be tested in mice neural cultures in the lab – effectively, models of the CLN6 mouse brain that can replicate some of the changes associated with Batten disease which will aid the team in gaining a greater understanding as to whether the proteins will adequately cross-correct other cells and therefore wider regions of the brain.

Dr Hughes and her team’s novel gene-therapy has the potential to solve the problem associated in the sheep model and bring this therapy closer to human trials – and closer to saving lives.