Trinity team’s gene therapy offers promise for treating glaucoma – as well as AMD

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A team of researchers at Trinity College in Dublin has developed a highly promising gene therapy to treat glaucoma, which affects around 80 million people worldwide.

The researchers previously showed their therapy offered promise in treating dry age-related macular degeneration (AMD), according to a news release.¹

The researchers have published their findings in the International Journal of Molecular Genetics. Their research shows how the gene therapy conferred significant benefit in animal models, and in human cells derived from people with glaucoma. 

Specifically, the therapy protected key “retinal ganglion cells” (RGCs) that are important in vision and improved their function in an animal model of glaucoma. In human retinal cells, delivery of the gene therapy increased oxygen consumption and ATP (energy) production, indicating enhanced cell performance.

Sophia Millington-Ward, PhD, the first author of the published research article, Research Fellow in Trinity’s School of Genetics and Microbiology, pointed out in a news release that glaucoma is a complex group of optic neuropathies and a leading cause of blindness.

“In Europe, roughly 1 in 30 people aged between 40 and 80 years have glaucoma, and that rises to 1 in 10 in persons over 90, so this is a really common condition that badly needs new treatment options,” she said in the news release. “It is a multifactorial condition with many different risk factors, which adds to the complexity of treating it. Current glaucoma treatments focus on the use of topical eye drops, surgery, or laser therapy, however the outcomes are variable, with some patients not responding and/or suffering serious side effects.”

Millington-Ward added the need for better treatment options has inspired and motivated researchers to continue developing gene therapies, she noted the team is delighted with the promise it is showing.”

The new gene therapy uses an approved virus to deliver an enhanced gene (eNdi1) developed by the Trinity team. The therapy was designed with the aim of boosting mitochondrial activity (mitochondria are “cellular energy generators” responsible for ATP production) and reducing damaging reactive oxygen species.¹

Jane Farrar, Research Professor in Trinity’s School of Genetics and Microbiology at Trinity, is the senior author of the published research article.

“Developing broadly applicable gene therapies for large numbers of patients is particularly important, given high development costs associated with each therapy – and here we have highlighted this therapy has real potential for boosting mitochondrial function in glaucoma,” she explained.

Translation of the studies to the clinic and patients, while involving many additional steps, is the next focus.

In the wake of the research milestones, Trinity’s researchers have teamed up with Loretto Callaghan to found Vzarii Therapeutics to expedite future development of the dry AMD and glaucoma gene therapies towards human clinical trials.²

According to the Trinity College news release, the research was funded by Science Foundation Ireland, Enterprise Ireland, Health Research Board Ireland, EU Marie Curie Innovative Training Network, and Fighting Blindness Ireland—Health Research Charities Ireland.

References:

1. Millington-Ward S, Palfi A, Shortall C, et al. AAV-NDI1 Therapy Provides Significant Benefit to Murine and Cellular Models of Glaucoma. International Journal of Molecular Sciences. 2024;25(16):8876-8876. doi:https://doi.org/10.3390/ijms25168876

2. Trinity College Dublin. Trinity team’s gene therapy offers promise for treating glaucoma – as well as AMD. Www.tcd.ie. Published 2024. Accessed September 9, 2024. https://www.tcd.ie/news_events/top-stories/featured/trinity-teams-gene-therapy-offers-promise-for-treating-glaucoma--as-well-as-amd-/