Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne
| Autor: | S. de Kimpe, D. de Klerk, Monika Hiller, Jan J.G.M. Verschuuren, Annemieke Aartsma-Rus, R. Jean-Baptiste, Francesco Muntoni, Mar Tulinius, Afrodite Lourbakos, Peter Nilsson, Zaïda Koeks, K. Kozaczynska, G. Campion, Nathalie Goemans, Pietro Spitali, Burcu Ayoglu, Ron Wolterbeek, Vishna Devi Nadarajah, N. Yau, Peter A C 't Hoen, Erik H. Niks, Mojgan Reza, Hanns Lochmüller, P. de Bruijn, C. Al-Khalili Szigyarto, Irina Zaharieva |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty Adolescent government.form_of_government Duchenne muscular dystrophy Placebo-controlled study lcsh:Medicine Muscle disorder Article Dystrophin 03 medical and health sciences Young Adult 0302 clinical medicine Double-Blind Method Internal medicine Medicine Humans Longitudinal Studies Muscular dystrophy lcsh:Science Child Drisapersen Randomized Controlled Trials as Topic Antisense therapy Multidisciplinary biology business.industry lcsh:R Exons Oligonucleotides Antisense medicine.disease Clinical trial Muscular Dystrophy Duchenne 030104 developmental biology Clinical Trials Phase III as Topic Matrix Metalloproteinase 9 Child Preschool government biology.protein lcsh:Q Female business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Scientific Reports Scientific Reports, 7 Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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