226th ENMC International Workshop: towards validated and qualified biomarkers for therapy development for Duchenne muscular dystrophy 20–22 January 2017, Heemskerk, The Netherlands

This report reflects the state-of-the-art and future directions of basic and clinical research into biomarkers for Duchenne Muscular Dystrophy (DMD), as discussed during the 204th ENMC workshop in Naarden, from January 24-26, 2014. Biomarkers have been defined as cellular, biochemical, molecular alterations or biological characteristics that are measurable in biological material as indicator of normal biological or pathogenic processes [1]. Biomarkers may be used in differential and early diagnosis, and in monitoring of disease progression, regression, or therapeutic responses. Duchenne Muscular Dystrophy (DMD) is a severe hereditary muscle disorder due dystrophin gene mutations and presenting with variable clinical severity [2]. Recently novel experimental drugs have been developed for DMD and several trials are ongoing, raising the urgent need of having fine tools for measuring trial outcomes as well as for optimizing the selection of eligible patients [3,4]. The use of clinical parameters measuring muscle strength and function is limited due to their dependence on motivation, large intra-individual variability, lack of linear relationship between the 2 and slow response time [5]. Conversely, molecular biomarkers may show earlier response to treatment and reflect the different pathophysiological aspects of the disease [6]. The use of biomarker panels for the diagnosis, prognosis, and monitoring of DMD (and more in general of rare chronic neuromuscular disorders or NMDs) as well as to guide the choice of therapeutic regimens may significantly improve the current clinical practice, by facilitating the evaluation of emerging therapies in drug trials and their regulatory approval. On the other hand, during the drug development process, the availability of a biomarker able to predict drug response and/or occurrence of adverse events could be of utmost importance and could also reduce the costs of the drug development [7]. Biomarkers can also serve for patient stratification and selection of appropriate subjects for clinical trials. Biomarkers can therefore have a positive impact on the economical load, patients’ care and novel therapies.