News & Views | Published:

NEUROMUSCULAR DISEASE

Why dystrophin quantification is key in the eteplirsen saga

Nature Reviews Neurologyvolume 14pages454456 (2018) | Download Citation

Eteplirsen, a compound designed to restore dystrophin in patients with Duchenne muscular dystrophy, controversially received approval by the FDA in 2016. Owing to limited clinical data, the approval was based on eteplirsen’s effect on dystrophin expression. Now, the dystrophin quantification results have been published, and although low levels of dystrophin expression are shown, the quantification remains debatable.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Aartsma-Rus, A. & Krieg, A. M. FDA approves eteplirsen for Duchenne muscular dystrophy: the next chapter in the eteplirsen saga. Nucleic Acid. Ther. 27, 1–3 (2017).

  2. 2.

    Charleston, J. S. et al. Eteplirsen treatment for Duchenne muscular dystrophy: exon skipping and dystrophin production. Neurology https://doi.org/10.1212/WNL.0000000000005680 (2018).

  3. 3.

    Schnell, F. et al. Development of a validated Western blot method for quantification of human dystrophin protein used in phase II and III clinical trials of eteplirsen for the treatment of Duchenne muscular dystrophy (DMD) (P5.105). Neurology 88, S16 (2017).

  4. 4.

    Anthony, K. et al. Dystrophin quantification: biological and translational research implications. Neurology 83, 2062–2069 (2014).

  5. 5.

    Arechavala-Gomeza, V. et al. Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: implication for clinical trials. Neuromuscul. Disord. 20, 295–301 (2010).

  6. 6.

    van Putten, M. et al. Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice. FASEB J. 27, 2484–2495 (2013).

Download references

Author information

Affiliations

  1. Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands

    • Annemieke Aartsma-Rus
  2. Neuromuscular Disorders Group, Biocruces Health Research Institute, Barakaldo, Spain

    • Virginia Arechavala-Gomeza

Authors

  1. Search for Annemieke Aartsma-Rus in:

  2. Search for Virginia Arechavala-Gomeza in:

Competing interests

A.-A.R. discloses being employed by Leiden University Medical Center (LUMC), which has patents on exon skipping technology, some of which has been licensed to BioMarin and subsequently sublicensed to Sarepta. As co-inventor of some of these patents A.-A.R. is entitled to a share of royalties. A.-A.R. further discloses being ad hoc consultant for PTC Therapeutics, BioMarin Pharmaceuticals Inc., Global Guidepoint and GLG consultancy, Grunenthal, Wave and BioClinica, having been a member of the Duchenne Network Steering Committee (BioMarin) and being a member of the scientific advisory boards of ProQR, MirrX therapeutics and Philae Pharmaceuticals. Remuneration for these activities is paid to LUMC. LUMC also received speaker honoraria from PTC Therapeutics and BioMarin Pharmaceuticals. V.A.G. has no competing interests.

Corresponding author

Correspondence to Annemieke Aartsma-Rus.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/s41582-018-0033-8

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing