Emerging Oligonucleotide Therapeutics for Rare Neuromuscular Diseases

Research and drug development concerning rare diseases are at the cutting edge of scientific technology. To date, over 7,000 rare diseases have been identified. Despite their individual rarity, 1 in 10 individuals worldwide is affected by a rare condition. For the majority of these diseases, there is no treatment, much less cure; therefore, there is an urgent need for new therapies to extend and improve quality of life for persons who suffer from them. Here we focus specifically on rare neuromuscular diseases. Currently, genetic medicines using short antisense oligonucleotides (ASO) or small interfering ribonucleic acids that target RNA transcripts are achieving spectacular success in treating these diseases. For Duchenne muscular dystrophy (DMD), the state-of-the-art is an exon skipping therapy using an antisense oligonucleotide, which is prototypical of advanced precision medicines. Very recently, golodirsen and viltolarsen, for treatment of DMD patients amenable to skipping exon 53, have been approved by regulatory agencies in the USA and Japan, respectively. Here, we reviewscientific and clinical progress in developing newoligonucleotide therapeutics for selected rare neuromuscular diseases, discussing their efficacy and limitations.

Automated summary

Research and drug development for rare diseases are crucial, affecting 1 in 10 individuals worldwide. Utilizing ASO and small interfering ribonucleic acids has been successful in treating rare neuromuscular diseases, particularly in exon skipping therapy.