John A Loudon
The burden of inherited diseases in terms of congenital defects and cancer predisposition in addition to a multitude of neurological, cardiovascular and other organ diseases arising sporadically during life is enormous on the individual, immediate family and society globally. I approach this major burden to human society by invoking the powerful technology behind read-through, whereby disease-causing substitution nonsense mutations, oftentimes at the root of human diseases, are rescued. Further, the importance of nonsense mutations in the realm of developmental factors linked to cancer stem cell maintenance is presented. The methodology behind the technique is given and proof of concept behind its use ex vivo and in clinical trials. The discovery of a novel read-through drug, Amlexanox, which has been in use for over twenty years in dentistry for oral ulcerations, represents a next generation read-through agent. This agent has been demonstrated in cell lines to correct functional loss in cystic fibrosis CFTR, dystrophin and the tumour suppressor, p53. Its novel ability to inhibit nonsense mediated decay is discussed. Amlexanox is therefore presently ready for testing in a wide variety of in vivo models of human diseases and also in clinical trials. Given the safety profile of Amlexanox and ex vivo efficacy in studies thus far it is envisaged that this accepted medication shall successfully debut as an all-purpose agent for the prevention and management of human diseases.
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