Researchers have discovered two new compounds that could potentially treat retinitis pigmentosa, a collection of hereditary eye disorders that lead to blindness. These compounds were found through a virtual screening method, as detailed in a study published on January 14 in the open-access journal PLOS Biology by Beata Jastrzebska from Case Western Reserve University, along with her team.
Retinitis pigmentosa often involves the misfolding of the retina protein rhodopsin due to genetic mutations. This misfolding causes retinal cells to deteriorate, leading to progressive blindness. There is an urgent need for small molecules that can correctly refold rhodopsin to help the approximately 100,000 people in the United States affected by this condition. Current experimental therapies tend to use retinoid compounds, such as synthetic vitamin A derivatives, which are light-sensitive and may be toxic, presenting several challenges.
In their recent study, the researchers employed virtual screening to identify new drug-like molecules that can bind to rhodopsin, helping to stabilize its structure and facilitate its proper folding and transport within the cell. They discovered two non-retinoid compounds that fulfilled these criteria and could efficiently cross the blood-brain and blood-retina barriers. Laboratory tests revealed that these compounds enhanced the surface expression of rhodopsin in 36 out of 123 different genetic variants of retinitis pigmentosa, including the most prevalent variant. Furthermore, these compounds offered protection against retinal degeneration in mice modeled after the disease.
The authors state, “Notably, treatment with either compound enhanced the overall health and functioning of the retina in these mice by extending the lifespan of their photoreceptors.” However, they emphasize that further research on these compounds, or similar ones, is necessary before initiating trials in humans.
According to the authors, “Inherited mutations in the rhodopsin gene lead to retinitis pigmentosa (RP), a progressive and currently untreatable condition resulting in blindness. This study identifies small molecule pharmacochaperones that mitigate the harmful effects of various rhodopsin mutations in vitro and reduce photoreceptor cell death in a mouse model of RP, presenting a promising new therapeutic path to prevent vision loss.”
