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

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

Badrising, UA, Tsonaka, R, Hiller, M, Niks, EH, Evangelista, T, Lochmüller, H et al.. Cytokine Profiling of Serum Allows Monitoring of Disease Progression in Inclusion Body Myositis. J Neuromuscul Dis. .4 (4)327-335 PMID:29172005

Lochmüller, H, Torrent I Farnell, J, Le Cam, Y, Jonker, AH, Lau, LP, Baynam, G et al.. The International Rare Diseases Research Consortium: Policies and Guidelines to maximize impact. Eur. J. Hum. Genet. 2017.25 (12)1293-1302 PMID:29158551

Reza, M, Cox, D, Phillips, L, Johnson, D, Manoharan, V, Grieves, M et al.. MRC Centre Neuromuscular Biobank (Newcastle and London): Supporting and facilitating rare and neuromuscular disease research worldwide. Neuromuscul. Disord. 2017.27 (11)1054-1064 PMID:28864117

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