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January 15, 2025 – Researchers have identified two promising compounds that may offer new hope for individuals suffering from retinitis pigmentosa (RP), a group of inherited eye diseases that lead to progressive blindness. The findings, published on January 14 in the open-access journal PLOS Biology, are the result of a virtual screening approach conducted by Beata Jastrzebska and her team at Case Western Reserve University, USA.
Retinitis pigmentosa affects approximately 100,000 people in the United States, primarily due to genetic mutations that cause misfolding of rhodopsin, a critical protein in the retina. This misfolding results in the death of retinal cells, ultimately leading to vision loss. Current experimental treatments, such as synthetic vitamin A derivatives, come with significant drawbacks, including light sensitivity and potential toxicity.
The new study employed virtual screening techniques to identify drug-like molecules capable of binding to and stabilizing rhodopsin, enhancing its folding and intracellular movement. This approach led to the discovery of two non-retinoid compounds that not only met these criteria but also demonstrated the ability to cross critical biological barriers, such as the blood-brain and blood-retina barriers.
Laboratory tests revealed that these compounds improved rhodopsin expression in 36 out of 123 genetic subtypes of retinitis pigmentosa, including the most common subtype. Moreover, experiments on mice with retinitis pigmentosa showed that the compounds protected against retinal degeneration and improved overall retina health and function.
“Importantly, treatment with either compound improved the overall retina health and function in these mice by prolonging the survival of their photoreceptors,” the authors reported. Despite these promising results, the researchers emphasized the need for further studies before moving to human trials.
The study highlights the potential of small molecule pharmacochaperones to suppress the harmful effects of rhodopsin mutations, offering a groundbreaking therapeutic strategy to slow photoreceptor cell death and prevent vision loss in retinitis pigmentosa patients.
More information about this breakthrough study can be found in PLOS Biology (2025), DOI: 10.1371/journal.pbio.3002932.
This development brings new optimism to the search for effective treatments for inherited blinding diseases, opening the door for innovative therapeutic approaches that could transform the lives of those affected.
