Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

NEUROMUSCULAR DISEASE

Why dystrophin quantification is key in the eteplirsen saga

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 options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Assessment of clinical benefit by eteplirsen.

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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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).

    Google Scholar 

  4. 4.

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

    Article  PubMed  PubMed Central  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Annemieke Aartsma-Rus.

Ethics declarations

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Aartsma-Rus, A., Arechavala-Gomeza, V. Why dystrophin quantification is key in the eteplirsen saga. Nat Rev Neurol 14, 454–456 (2018). https://doi.org/10.1038/s41582-018-0033-8

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

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