New gene therapy shows promise for treating glaucoma – as well as AMD

Scientists at Trinity College Dublin have developed a promising gene therapy to treat glaucoma, a debilitating eye disease that can lead to total vision loss and affects around 80 million people worldwide. The team had previously shown promise in treating dry age-related macular degeneration (AMD).

The scientists have just published their research in the International Journal of Molecular GeneticsTheir work shows how gene therapy has conferred significant benefits in animal models and in human cells derived from people with glaucoma.

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

Lead author of the published research paper, Dr Sophia Millington-Ward, a research fellow in Trinity’s School of Genetics and Microbiology, said: “Glaucoma is a complex group of optic neuropathies and a leading cause of blindness. In Europe, around 1 in 30 people aged 40 to 80 have glaucoma, rising to 1 in 10 in people over 90. This makes it a very common disease that urgently needs new treatment options.”

“It is a multifactorial disease with many different risk factors, which adds to the complexity of its treatment. Current treatments for glaucoma focus on the use of topical eye drops, surgery or laser therapy, but results 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, and we are excited about the promise they hold.”

The new gene therapy uses an approved virus to deliver an enhanced gene (eNdi1) developed by the Trinity team. The therapy was designed to boost mitochondrial activity (mitochondria are cellular “powerhouses” responsible for producing ATP) and reduce harmful reactive oxygen species.

Jane Farrar, Research Professor in Trinity’s School of Genetics and Microbiology, is the lead author of the published research paper. She added:

“The development of gene therapies that are broadly applicable to a large number of patients is particularly important, given the high development costs associated with each therapy. Here, we have highlighted that this therapy has real potential to stimulate mitochondrial function in glaucoma.”

Translating studies to the clinic and patients, while involving many additional steps, is the next goal.

Building on these and other foundational achievements, the Trinity team – in collaboration with Loretto Callaghan – recently founded Vzarii Therapeutics to accelerate the future development of gene therapies for dry AMD and glaucoma into human clinical trials.