New results for golodirsen in DMD demonstrate a tendency to protect muscle from degeneration

The golodirsen (Vyondys 53 – SRP-4053) antisense oligonucleotide (Sarepta Therapeutics) targeting exon 53 skipping of the dystrophin gene (DMD gene) has been authorised in the United States in Duchenne muscular dystrophy (DMD) since February 2020.

New data from the phase I/II trial of golodirsen (which ended in 2019) has just been published in the journal Acta Neuropathologica Communication.

This international trial related to 25 boys with DMD, aged 6 to 15 years, treated for over two and a half years with golodirsen, at a rate of one injection per week.

The latest results that have appeared relate to the analysis by immunofluorescence of several muscle proteins, based on muscle biopsies from 25 trial participants, taken 48 weeks after treatment, for the purpose of establishing a relationship  with the dystrophin activity produced by the exon skipping.

The following were analysed:

  • α-sarcoglycan and β-dystroglycan (and laminin α2);
  • immature (foetal and developmental) forms of myosin (f/d myosin).


Increase in β-dystroglycan where dystrophin is present

Biopsy immunofluorescence testing does not show a significant change in the levels of the proteins associated with dystrophin: α-sarcoglycan and β-dystroglycan were already present before treatment. However, finer testing of the sarcolemma areas shows that where dystrophin is present, β-dystroglycan levels are significantly increased, unlike the membranous areas where it was not present.


Degeneration decreased in the muscles of certain patients

For participants as a whole, the mean levels of f/d myosin, viewed under fluorescence microscopy, after 48 weeks of treatment with golodirsen, did not change significantly.

However, the change in f/d myosin levels diverged significantly between participants: it decreased by a mean of 7.1% for half of them (12/24), increased by a mean of 4.3% for one third of them (8/24) and stayed the same for the remainder (4 patients).

The authors showed that in the majority of patients with a high level of dystrophin (measured by immunofluorescence), the level of f/d myosin was lower, indicating a certain degree of functionality of the dystrophin synthesised by exon skipping.

These results indicate that newly produced dystrophin would seem to be functional in the muscle cells where it is present. Additional studies are needed to confirm these data over the long-term and to evaluate the functional impact.


The administration of antisense oligonucleotide golodirsen reduces pathological regeneration in patients with Duchenne muscular dystrophy. Scaglioni D, Catapano F, Ellis M, Torelli S, Chambers D, Feng L, Beck M, Sewry C, Monforte M, Harriman S, Koenig E, Malhotra J, Popplewell L, Guglieri M, Straub V, Mercuri E, Servais L, Phadke R, Morgan J, Muntoni F.  Acta Neuropathol Commun. 2021 Jan 6;9(1):7.