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

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. 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

Walter, MC, Wenninger, S, Thiele, S, Stauber, J, Hiebeler, M, Greckl, E et al.. Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3 - A Prospective Observational Study. J Neuromuscul Dis. 2019.6 (4)453-465 PMID:31594243

Coenen-Stass, AML, Sork, H, Gatto, S, Godfrey, C, Bhomra, A, Krjutškov, K et al.. Comprehensive RNA-Sequencing Analysis in Serum and Muscle Reveals Novel Small RNA Signatures with Biomarker Potential for DMD. Mol Ther Nucleic Acids. 2018.13 1-15 PMID:30219269

Spitali, P, Hettne, K, Tsonaka, R, Charrout, M, van den Bergen, J, Koeks, Z et al.. Tracking disease progression non-invasively in Duchenne and Becker muscular dystrophies. J Cachexia Sarcopenia Muscle. 2018.9 (4)715-726 PMID:29682908

Sarkozy, A, Torelli, S, Mein, R, Henderson, M, Phadke, R, Feng, L et al.. Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy. J. Neurol. Neurosurg. Psychiatry. 2018.89 (7)762-768 PMID:29437916

Lourbakos, A, Yau, N, de Bruijn, P, Hiller, M, Kozaczynska, K, Jean-Baptiste, R et al.. Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne. Sci Rep. 2017.7 (1)17888 PMID:29263366

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