Testing the efficacy of Ataluren on restoring dysferlin expression and function in a mouse model
Recent efforts to develop therapeutic strategies for the treatment of some forms of muscular dystrophy have focused on various approaches to allow for read-through of premature stop codons and similar variations that alter the expression of genes relating to muscular dystrophy. These approaches attempt to avoid the effects of a single nucleotide in the DNA sequence that encodes for a protein. Presence of this non-sense mutation may completely disrupt the reading frame of the protein and produce an incomplete, non-functional truncated protein. Extensive pre-clinical and clinical studies have shown that ataluren, also known as PTC124, increases read-through the nonsense stop codon to produce functional transcripts. This drug has been tested for its efficacy and safety in a number of models of muscular dystrophy and is now under clinical evaluation with over two dozen clinical trials either completed or underway in a variety of genetic disorders. In this project we will evaluate the efficacy of ataluren to induce the production of functional dysferlin protein in a mouse model of LGMD2B.