Scientists develop new gene therapy for eye disease

November 26, 2020

Scientists from Trinity College Dublin have developed a new gene therapy approach that offers promise for one day treating an eye disease that leads to a progressive loss of vision and affects thousands of people across the globe.

The study, which involved a collaboration with clinical teams in the Royal Victoria Eye and Ear Hospital and the Mater Hospital, also has implications for a much wider suite of neurological disorders associated with ageing.

The scientists publish their results today [Thursday 26th November 2020] in leading journal, Frontiers in Neuroscience.

Dominant optic atrophy (DOA)

Characterised by degeneration of the optic nerves, 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 DOA.

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 sub-optimal and the mitochondrial network which in healthy cells is well interconnected is highly disrupted.

For those living with DOA, it is mutations in OPA1 and the dysfunctional mitochondria that are responsible for the onset and progression of the disorder.

The new gene therapy

The scientists, led by Dr Daniel Maloney and Professor Jane Farrar from Trinity's School of Genetics and Microbiology, 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, offering hope that it may be effective in people.

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."

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.

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.

"OPA1 mutations are involved in DOA and so this OPA1-based therapeutic approach is relevant to DOA. However mitochondrial dysfunction is implicated in many neurological disorders that collectively affect millions of people worldwide. We think there is great potential for this type of therapeutic strategy targeting mitochondrial dysfunction to provide benefit and thereby make a major societal impact. 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."
-end-
The research was supported by Science Foundation Ireland, the Health Research Board of Ireland, Fighting Blindness Ireland, and the Health Research Charities Ireland.

A copy of the journal article is available on request.

Trinity College Dublin

Related Gene Therapy Articles from Brightsurf:

Risk of AAV mobilization in gene therapy
New data highlight safety concerns for the replication of recombinant adeno-associated viral (rAAV) vectors commonly used in gene therapy.

Discovery challenges the foundations of gene therapy
An article published today in Science Translational Medicine by scientists from Children's Medical Research Institute has challenged one of the foundations of the gene therapy field and will help to improve strategies for treating serious genetic disorders of the liver.

Gene therapy: Novel targets come into view
Retinitis pigmentosa is the most prevalent form of congenital blindness.

Gene therapy targets inner retina to combat blindness
Batten disease is a group of fatal, inherited lysosomal storage disorders that predominantly affect children.

New Human Gene Therapy editorial: Concern following gene therapy adverse events
Response to the recent report of the deaths of two children receiving high doses of a gene therapy vector (AAV8) in a Phase I trial for X-linked myotubular myopathy (MTM).

Restoring vision by gene therapy
Latest scientific findings give hope for people with incurable retinal degeneration.

Gene therapy/gene editing combo could offer hope for some genetic disorders
A hybrid approach that combines elements of gene therapy with gene editing converted an experimental model of a rare genetic disease into a milder form, significantly enhancing survival, shows a multi-institutional study led by the University of Pennsylvania and Children's National Hospital in Washington, D.C.

New technology allows control of gene therapy doses
Scientists at Scripps Research in Jupiter have developed a special molecular switch that could be embedded into gene therapies to allow doctors to control dosing.

Gene therapy: Development of new DNA transporters
Scientists at the Institute of Pharmacy at Martin Luther University Halle-Wittenberg (MLU) have developed new delivery vehicles for future gene therapies.

Gene therapy promotes nerve regeneration
Researchers from the Netherlands Institute for Neuroscience and the Leiden University Medical Center have shown that treatment using gene therapy leads to a faster recovery after nerve damage.

Read More: Gene Therapy News and Gene Therapy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.