Potential drug targets identified for RP
A recent study reveals shared disease mechanisms in inherited sight loss, suggesting potential drug treatments that could be effective across different genetic causes.
A recently published study has described numerous disease mechanisms that appear to be common across different types of inherited sight loss, suggesting that there is significant potential for drug treatments that could work regardless of the underlying causative gene.
The researchers in Finland, Canada and the USA undertook a detailed investigation of the molecular pathways at play in three different mouse models of inherited retinal conditions: a model of recessively inherited retinitis pigmentosa (RP) caused by the PDE6B gene, a model of dominant RP caused by the RHO gene, and a model of Leber congenital amaurosis (LCA) caused by the RPE65 gene.
The researchers employed “proteomics”, the study of the entire range of proteins present in cells, to understand all the knock-on effects occurring as a consequence of the underlying genetic fault. This enabled them to see where disease mechanisms converged in the different models.
They discovered that the two RP models displayed a huge number of commonalities, suggesting various critical pathways that could be targeted by drugs in order to slow or stop disease progression regardless of the underlying genetic mutation. The LCA model mouse had far less in common with the other two, although there were still some areas of overlap, including inflammatory and cell stress-related processes.
The researchers caution that the mouse models have limitations and that lots of further work is needed, but some of their findings are supported by results from other studies.
Edinburgh-based researcher and ophthalmologist Dr Roly Megaw has previously delivered a Retina UK webinar about inflammation and its potential as a treatment target; you can find the recording at Webinar: Inflammation and retinal degeneration in RP – Retina UK .
Prof Jacqueline van der Spuy at UCL’s Institute of Ophthalmology is currently undertaking a Retina UK-funded project looking at a molecule called cGMP, which this recent study identified as a common factor across disease types. You can find out more about our current projects at: Research grants – Retina UK .