Translational readthrough inducing drugs for the treatment of inherited retinal dystrophies.

Inherited retinal disorders (IRDs) are the most common cause of certifiable blindness in working-age adults in the UK. There are currently no treatments for the majority of patients, resulting in considerable morbidity with lifelong socioeconomic implications. Twelve percent of all genetic disease variants are nonsense mutations, which encode a premature termination codon (PTC). The resultant transcript is either degraded through nonsense-mediated decay (NMD) or translated into a truncated protein. Nonsense suppression therapy aims to bypass and allow translation beyond the PTC, creating a full-length protein and possible phenotypic rescue. The responsible agents, named translational readthrough-inducing drugs (TRIDs), have been in continuous development to maximize efficiency and minimize toxicity. These include aminoglycosides, aminoglycoside derivatives and non-aminoglycoside small molecule drugs and have been successfully applied to a number of diseases in recent preclinical studies. This review provides an update in the advancements of nonsense suppression therapy in the treatment of IRDs, including an overview of this process and NMD, advancements in the development of TRIDs and barriers to clinical trials including drug developments, disease modeling, and patient selection. Clinical trials are forthcoming for patients with IRDs to determine TRIDs suitability as viable therapy options. [ABSTRACT FROM AUTHOR]