Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne

Sci Rep. 2017 Dec 20;7(1):17888. doi: 10.1038/s41598-017-17982-y.


Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood*
  • Child
  • Child, Preschool
  • Clinical Trials, Phase III as Topic
  • Double-Blind Method
  • Dystrophin / genetics
  • Exons / genetics
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Muscular Dystrophy, Duchenne / blood*
  • Muscular Dystrophy, Duchenne / genetics*
  • Oligonucleotides, Antisense / genetics*
  • Randomized Controlled Trials as Topic
  • Young Adult


  • Biomarkers
  • Dystrophin
  • Oligonucleotides, Antisense
  • Matrix Metalloproteinase 9