Non-viral gene therapy for Ataxia Telangiectasia

Research Project information

Principal researcher: Dr James Dixon
Institute: University of Nottingham
Cost: ~£105,000 over 24 months in partnership with A-TCP
Start Date: September 2018

Action for A-T has provided £50,000 towards this project which is being funded and managed by the US based A-T Children’s Project.

What are the researchers proposing to do?

Non-viral gene therapy has the potential to safely and cheaply deliver new copies of genes to correct neurodegenerative disorders such as Ataxia Telangiectasia (A-T). Dr Dixon (University of Nottingham, UK) and his team aim to develop and then deploy a system to supply new ATM genes (the gene mutated in A-T patients) and provide a universal therapy for many aspects of the disease, but specifically in this grant the neurodegeneration seen in the brain (cerebellum).

Why?

There are currently no effective treatments for A-T, and the size of the ATM gene poses challenges to traditional virus-mediated gene replacement therapy approaches. A new peptide-based gene therapy technology has recently been developed by the Nottingham group, which has been demonstrated effective at delivering new genes in the lung and to bone in trauma. By applying the technology to A-T therapy, a treatment could be developed that could be used to treat different aspects of the disease in all A-T patients.

How will the research be done?

The team will re-engineer a full-length ATM gene both to make it express the missing protein strongly and to make it resistant to being ‘turned off’ prematurely. These new genes will be packaged into Dr. Dixon’s system and tested for activity in patient cells culture and in models of A-T. The team will attempt to deliver the therapy by directly injecting into the brain or through less invasive routes such as lumbar puncture to reach and correct gene defect in the cerebellum.

How could it make a difference to the lives of those affected by A-T?

The initial aim is delivery of synthetic ATM genes into neurons in the brain’s cerebellum because they seem to be most affected by the loss of the ATM protein. The objective would be to slow or halt the ataxia and other movement disorders in all A-T patients. While this is still the central aim of Dr. Dixon’s work, the engineered ATM gene delivery system could be used to address the lung infection and cancer symptoms of A-T.