Nonsense Tx reading through disease causing nonsense codons
Investment summary
Nonsense mutations cause premature termination codons (PTCS), resulting in premature termination of translation. Proteins made from genes with nonsense mutations are produced in a truncated, non-functional form, leading to diseases including RDEB. Nonsense mutations are found in approximately one third of RDEB patients.
Certain compounds are recognized for their ability to facilitate nonsense (PTC) readthrough, a process allowing the production of the complete protein despite the presence of nonsense mutations. For example, aminoglycoside antibiotics, which have been tested on a limited number of RDEB patients, have the ability to enhance the production of collagen VII and improve patient symptoms. However, the doses required lead to toxicity concerns which limit their practical use. Other compounds promote nonsense readthrough via different mechanism.
In preliminary work conducted on isolated patient cells, it was shown that some of these compounds significantly potentiate the efficiency of nonsense readthrough in conjunction with aminoglycosides. This enhancement allows for effective results at concentrations up to 10x lower, where toxicity becomes a non-issue. Building on these research findings, the company plans to explore this combinational approach by optimizing the properties of these compounds.