Biomarker discovery and validation

The National Institutes of Health’s Biomarkers Definitions Working Group defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Biomarkers have become an important read-out measure to study the therapeutic effect of drugs in clinical trials, in particular to show effect at an earlier stage than clinical outcome measures. By definition objective, quantifiable characteristics of biological processes, biomarkers must reliably show change in response to the process or intervention being measured, and in many cases this has been lacking in neuromuscular disease.

The discovery, definition and validation of reliable and sensitive blood, cell and tissue-related biomarkers is therefore an important goal of our lab’s research, since it is a foundation for diagnosis, monitoring of disease progression, and evaluation of potential therapy for our diseases of interest. Our group has worked on biomarkers for Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1) and GNE myopathy at both the biochemical and molecular genetic level. We have defined markers that show consistent and significant correlation with disease severity, and are working to take this research forward in larger cohorts.


Healthcare professional taking a blood sample from an arm

Relevant publications

Landfeldt, E, Alemán, A, Abner, S, Zhang, R, Werner, C, Tomazos, I et al.. Predictors of Loss of Ambulation in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis. J Neuromuscul Dis. 2024.11 (3)579-612 PMID:38669554

Smith, IC, Chakraborty, S, Bourque, PR, Sampaio, ML, Melkus, G, Lochmüller, H et al.. Emerging and established biomarkers of oculopharyngeal muscular dystrophy. Neuromuscul Disord. 2023.33 (11)824-834 PMID:37926637

Nguyen, CDL, Jimenez-Moreno, AC, Merker, M, Bowers, CJ, Nikolenko, N, Hentschel, A et al.. Periostin as a blood biomarker of muscle cell fibrosis, cardiomyopathy and disease severity in myotonic dystrophy type 1. J Neurol. 2023.270 (6)3138-3158 PMID:36892629

Melkus, G, Sampaio, ML, Smith, IC, Rakhra, KS, Bourque, PR, Breiner, A et al.. Quantitative vs qualitative muscle MRI: Imaging biomarker in patients with Oculopharyngeal Muscular Dystrophy (OPMD). Neuromuscul Disord. 2023.33 (1)24-31 PMID:36462961

van Cruchten, RTP, van As, D, Glennon, JC, van Engelen, BGM, 't Hoen, PAC, OPTIMISTIC consortium et al.. Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood. BMC Med. 2022.20 (1)395 PMID:36352383

Koutsoulidou, A, Koutalianos, D, Georgiou, K, Kakouri, AC, Oulas, A, Tomazou, M et al.. Serum miRNAs as biomarkers for the rare types of muscular dystrophy. Neuromuscul Disord. 2022.32 (4)332-346 PMID:35393236

Kakouri, AC, Koutalianos, D, Koutsoulidou, A, Oulas, A, Tomazou, M, Nikolenko, N et al.. Circulating small RNA signatures differentiate accurately the subtypes of muscular dystrophies: small-RNA next-generation sequencing analytics and functional insights. RNA Biol. 2022.19 (1)507-518 PMID:35388741

Schorling, DC, Kölbel, H, Hentschel, A, Pechmann, A, Meyer, N, Wirth, B et al.. Cathepsin D as biomarker in cerebrospinal fluid of nusinersen-treated patients with spinal muscular atrophy. Eur J Neurol. 2022.29 (7)2084-2096 PMID:35318785

Burch, PM, Pogoryelova, O, Goldstein, R, Bennett, D, Guglieri, M, Straub, V et al.. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy. J Neuromuscul Dis. 2015.2 (3)241-255 PMID:26870665

Ayoglu, B, Chaouch, A, Lochmüller, H, Politano, L, Bertini, E, Spitali, P et al.. Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014.6 (7)918-36 PMID:24920607