DMD is a severe X linked neuromuscular disorder where symptoms may arise as early as 2 years of age and patient surviving till adulthood is extremely rare. This is caused by mutations in dystrophin-a critical gene for muscle fibre strength- leading to a severe reduction of the dystrophin protein in muscles. A milder form DMD is Becker’s muscular dystrophy (BMD), caused by distinct mutations in the same gene which conserves some protein function. In recent years, the use of antisense oligonucleotides (AONs) as RNA-modulating therapeutics has made significant progress. An insight into the differential consequence of the distinct mutations on the same gene, researchers have developed AON’s that skips exon 51 in the dystrophin gene (like in BMD) and aids in conserving some of the protein function (observed in BMD patients) in patients suffering from DMD. The authors discuss the preclinical development of two antisense therapies- drisapersen and eteplirsen- two chemically distinct drug candidates that have demonstrated the features of exon 51 skipping. The authors believe in the potential of both drugs although both have “advantages and disadvantages with regard safety and pharmacokinetics”. The authors stress that “increasing lower prevalence of mutations, a non-standard, orphan drug-tailored design of clinical studies is required and they believe that the advent of the AON technology along with ongoing developments bring personalised medicine for these patients a reality”. This review provides an overview of the current developmental status of AONs for DMD and summarises the challenges and discussions for such personalised mutation-specific therapeutics progressing through the development pipeline.
