Researchers have developed a new gene therapy approach that shows promise for treating dry AMD by boosting the function of mitochondria, which power cells and are especially crucial in retinal cells.
The team, in Trinity College Dublin’s School of Genetics and Microbiology, have formulated a therapy called ophNdi1, described as the first of its kind to directly target mitochondrial function in cells that are malfunctioning in age-related macular degeneration (AMD).
Mitochondria are known as the “powerhouses” of the cell because they manage the production of energy but their performance dips greatly in dry AMD and this is linked to a deterioration in sight, the researchers stated.
With there being no approved treatments for dry age AMD – also known as geographic atrophy (GA) – it remains one of the most significant unmet needs in all retinal disease categories. Novartis recently acquired the most promising therapy in this space, GT005, which aims to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein.
The Trinity gene therapy uses a virus to access the cells that are suffering and deliver the code needed to give the failing mitochondria a lifeline, enabling them to generate extra energy and continue to function in supporting vision.
According to Trinity, the therapy has shown benefit in multiple models of dry AMD, offering hope that it could one day progress to a treatment that could help millions across the globe.
“Critically, this study provides the first evidence in models that directly modulating bioenergetics in eye cells can provide benefit and improve visual function in dry AMD. In doing so, the study highlights the energy powerhouses of the cell, mitochondria, as key targets for dry AMD,” Professor Jane Farrar, senior author, said.
Dr Sophia Millington-Ward, first author and Research Fellow in Trinity’s School of Genetics and Microbiology, said many retinal cells, essential for vision, require particularly high levels of energy compared to most other cells, which makes them particularly vulnerable to mitochondrial dysfunction.
“The therapy we are developing directly targets mitochondrial function and increases energy production levels in the retina, which leads to better visual function in disease models of dry AMD,” she said.
Although there is further work to be done before the therapy could be brought to market, Millington-Ward said the results “offer hope that we are getting closer to a solution to this challenging, debilitating condition”.
The work has just been published in the journal Clinical and Translational Medicine and can be accessed here.
Dry AMD cases represent around 85-90% of all AMD cases and there are no treatments available to treat or prevent disease progression, underlining the need for developing treatment options for this debilitating disease. In adults, many diseases of aging have been found to have defects of mitochondrial function, including AMD.
More reading
Novartis targets GA gene therapy in Gyroscope Therapeutics deal
Sydney surgeon details first Luxturna gene therapy allowing patient to see stars
