Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Lourbakos, A.; Yau, N.; de Bruijn, P.; Hiller, M.; Kozaczynska, K.; Jean-Baptiste, R.; Reza, M.; Wolterbeek, R.; Koeks, Z.; Ayoglu, B.; de Klerk, D.; Campion, G.; Zaharieva, I.; Nadarajah, V.; Nilsson, P.; Al-Khalili Szigyarto, C.; Muntoni, F.; Lochmüller, H.; Verschuuren, J.; Goemans, N.; Tulinius, M.; Niks, E.; de Kimpe, S.; Aartsma-Rus, A.; 't Hoen, Peter; Spitali, P.
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-17982-y
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract 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.