Scientists from Trinity College Dublin have developed a new gene therapy for an eye disease that leads to progressive loss of vision

The research team collaborated with clinical teams at the Royal Victoria Eye and Ear Hospital, and the Mater Hospital. The work they did together doesn’t only have implications for progressive blindness – but also for various neurological disorders that come with ageing populations.

What is dominant optic atrophy?

Characterised by degeneration of the optic nerves, dominant optic atrophy (DOA) typically starts to cause symptoms in patients in their early adult years. These include moderate vision loss and some colour vision defects, but severity varies, symptoms can worsen over time and some people may become blind. There is currently no way to prevent or cure this eye disease.

A gene (OPA1) provides instructions for making a protein that is found in cells and tissues throughout the body, and which is pivotal for maintaining proper function in mitochondria, which are the energy producers in cells. Without the protein made by OPA1, mitochondrial function is not good, and the mitochondrial network which in healthy cells is well interconnected is highly disrupted.

For those living with this eye disease, it is mutations in OPA1 and the dysfunctional mitochondria that are responsible for the disorder.

‘Specially engineered non-harmful viruses’

Dr Maloney, Research Fellow, said: “We used a clever lab technique that allows scientists to provide a specific gene to cells that need it using specially engineered non-harmful viruses. This allowed us to directly alter the functioning of the mitochondria in the cells we treated, boosting their ability to produce energy which in turn helps protects them from cell damage.

“Excitingly, our results demonstrate that this OPA1-based gene therapy can potentially provide benefit for diseases like DOA, which are due to OPA1 mutations, and also possibly for a wider array of diseases involving mitochondrial dysfunction.”

What is the new gene therapy?

The scientists have developed a new gene therapy, which successfully protected the visual function of mice who were treated with a chemical targeting the mitochondria and were consequently living with dysfunctional mitochondria. The scientists also found that their gene therapy improved mitochondrial performance in human cells that contained mutations in the OPA1 gene – meaning that this could also work in humans.

Professor Farrar, Research Professor, added: “We are very excited by the prospect of this new gene therapy strategy, although it is important to highlight that there is still a long journey to complete from a research and development perspective before this therapeutic approach may one day be available as a treatment.

“Having worked together with patients over many years who live with visual and neurological disorders it would be a privilege to play a role in a treatment that may one day help many.

Importantly, mitochondrial dysfunction causes problems in a suite of other neurological disorders such as Alzheimer’s and Parkinson’s disease. The impacts gradually build up over time, which is why many may associate such disorders with ageing.