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Lookup NU author(s): Dr Mojgan Reza,
Professor Hanns Lochmuller,
Professor Annemieke Aartsma-Rus
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 The Author(s). 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.
Author(s): 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 VD, Nilsson P, Al-Khalili Szigyarto C, Muntoni F, Lochmuller H, Verschuuren JJ, Goemans N, Tulinius M, Niks EH, De Kimpe S, Aartsma-Rus A, T'Hoen PAC, Spitali P
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Online publication date: 20/12/2017
Acceptance date: 04/12/2017
Date deposited: 10/01/2018
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
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