A. Lourbakos, N. Yau, P. de Bruijn, M. Hiller, K. Kozaczynska, R. Jean -Baptiste, M. Reza, R. Wolterbeek, Z. Koeks, B. Ayoglu, D. de Klerk, G. Campion, I. Zaharieva, V. D. Nadarajah, P. Nilsson , C. Al-Khalili Szigyarto, F. Muntoni, H. Lochmüller, J. J. Verschuuren, N. Goemans, M. Tulinius, E. H. Niks, S. de Kimpe, A. Aartsma-Rus, Peter A. C. ’t Hoe & P. Spitali
Scientific Reports, volume 7, issue Article number: 17888,
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.