New treatments in neuromuscular disorders

Abstract

Molecular treatments this group of disorders is approaching. Just to name a few: X-linked myotubular myopathy, myotonic dystrophy, Limb-girdle dystrophies and so on. The most advances are for Duchenne muscular dystrophy. Ataluren has now been approved by several countries. This is a mutation specific therapy (“stop codon read through”), affecting approximately 15% of the DMD population, and is an oral molecule taken daily. It is considered as a ‘disease modifying molecule’, hence should not be considered as a cure. Other therapeutic approaches currently tested in clinical trials include: mutation-specific strategies aiming to correct the underlying genetic cause of the disease (e.g. exon skipping). Eteplirsen is an antisense-oligonucleotide to skip exon 51 of the DMD gene. It is available on the market, however with reservations related to efficacy. Other anti-sense oligonucleotide drugs in the pipeline are Casimersen for exon 45, Golodirsen for exon 53, and Suvodirsen for exon 51 skipping, respectively. Among these Viltolarsen has been in the forefront with a backbone publication. Gene therapy can be considered on the horizon. One example is the micro-dystrophin gene delivered in AAV9 virus. Since 2018 four boys aged 4–6 were treated with gene therapy with an admirable improvement rate of 25–30% from the baseline. Curently there is a new series of boys with more than 60 subjects and this is ongoing. However, there are multi-fold hurdles with gene therapy to include the timing, dosage, remainings of the viral vector, burden on innate immunity, and availablity on national levels.