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

Regensburger, AP, Wagner, AL, Danko, V, Jüngert, J, Federle, A, Klett, D et al.. Multispectral optoacoustic tomography for non-invasive disease phenotyping in pediatric spinal muscular atrophy patients. Photoacoustics. 2022.25 100315 PMID:34849338

Koutalianos, D, Koutsoulidou, A, Mytidou, C, Kakouri, AC, Oulas, A, Tomazou, M et al.. miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1. Mol Ther Methods Clin Dev. 2021.23 169-183 PMID:34703840

McMillan, HJ, Lochmüller, H. Biomarkers in Duchenne and Becker muscular dystrophies. Muscle Nerve. 2021.64 (1)4-5 PMID:34076279

Grande, V, Hathazi, D, O'Connor, E, Marteau, T, Schara-Schmidt, U, Hentschel, A et al.. Dysregulation of GSK3β-Target Proteins in Skin Fibroblasts of Myotonic Dystrophy Type 1 (DM1) Patients. J Neuromuscul Dis. 2021.8 (4)603-619 PMID:33682722

Passarelli, C, Selvatici, R, Carrieri, A, Di Raimo, FR, Falzarano, MS, Fortunato, F et al.. Tumor Necrosis Factor Receptor SF10A (TNFRSF10A) SNPs Correlate With Corticosteroid Response in Duchenne Muscular Dystrophy. Front Genet. 2020.11 605 PMID:32719714

Thompson, R, Spendiff, S, Roos, A, Bourque, PR, Warman Chardon, J, Kirschner, J et al.. Advances in the diagnosis of inherited neuromuscular diseases and implications for therapy development. Lancet Neurol. 2020.19 (6)522-532 PMID:32470424

Strandberg, K, Ayoglu, B, Roos, A, Reza, M, Niks, E, Signorelli, M et al.. Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy. J Neuromuscul Dis. 2020.7 (3)231-246 PMID:32390640

Signorelli, M, Ayoglu, B, Johansson, C, Lochmüller, H, Straub, V, Muntoni, F et al.. Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy. J Cachexia Sarcopenia Muscle. 2020.11 (2)505-517 PMID:31881125

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