Outcome measures in muscle disorders

In recent years, significant progress has been made in development of candidate drugs and genetic therapies in distinct muscle disorders. One well-known example is the antisense oligonucleotide (AON) treatment for exon skipping in Duchenne muscular dystrophy. As candidate drugs enter clinical trials, it is critical to understand the natural history of the disease and use available data from natural history studies to evaluate clinical outcome measures for planned efficacy studies. Furthermore, a strong understanding of the natural history of the disease is essential to drug development in orphan muscle diseases, since the numbers of patients available for trials will be limited. For this purpose, we need reliable and reproducible outcome measures through objective biomarkers, either clinical, radiological and/or biochemical, that must be minimally invasive and feasible to use in daily clinical practice. Several clinical outcome measures already exist for many years, such as subjective manual muscle force grading systems (MRC sum score) and walking tests (Six-Minute Walking Distance, 6MWD). Novel disease-specific and reproducible clinical tests have been developed in the last decade, such as the North Star Ambulatory Assessment (NSAA) for Duchenne/Becker Muscular Dystrophy. Patient Reported Outcome Measures (PROMs), such as quality of life questionnaires or the ActivLim scale, have also been introduced and validated in clinical studies. Radiological outcome measures are still being developed and refined, with special focus on quantitative MR imaging. Finally, also biochemical markers of muscle disease progression are finding their way into clinical trials.