Trinity team’s gene therapy offers promising glaucoma and AMD treatment

The new gene therapy delivers an enhanced gene, eNdi1, via an approved virus. Image credit: ©Corona Borealis – stock.adobe.com

A team of researchers at Trinity College in Dublin, Ireland, has developed a highly promising gene therapy to treat glaucoma, which affects around 80 million people worldwide. Previously, investigations into the therapeutic demonstrated its potential for treating dry age-related macular degeneration (AMD), according to a news release about the research.¹

Sophia Millington-Ward, PhD, is the first author of the published research article and a Research Fellow in Trinity’s School of Genetics and Microbiology. Her team published its findings in the International Journal of Molecular Genetics. Their research shows how the gene therapy conferred significant benefit both 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.^1,2 In human retinal cells, delivery of the gene therapy increased oxygen consumption and ATP (energy) production, indicating enhanced cell performance.

The new gene therapy delivers an enhanced gene (eNdi1), developed by the Trinity team, via an approved virus. It was designed with the aim of boosting mitochondrial activity (“cellular energy,” as described by the research team) and reducing damaging reactive oxygen species.¹

In a news release, Millington-Ward described glaucoma as 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.”

“The need for better treatment options has inspired and motivated us to continue developing gene therapies,” Millington-Ward added. “We are delighted with the promise it is showing."

Jane Farrar, Research Professor in Trinity’s School of Genetics and Microbiology at Trinity and senior author of the research article, said the therapeutic has “real potential” for boosting mitochondrial function.

“Developing broadly applicable gene therapies for large numbers of patients is particularly important, given high development costs associated with each therapy,” she stated.

The investigators’ focus going forward will be translation of the study findings towards the clinical setting and treating patients, which is expected to involve many additional steps.

In the wake of the research milestones, Trinity’s researchers have teamed up with Loretto Callaghan, former CEO and director at Novartis in Ireland, to found Vzarii Therapeutics. The joint venture is hoped to expedite future development of the dry AMD and glaucoma gene therapies towards human clinical trials.1

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. 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-/

2. 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

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