Aartsma-Rus A, Morgan J, Lonkar P, et al. Report of a TREAT-NMD/World Duchenne Organisation Meeting on Dystrophin Quantification Methodology. Journal of neuromuscular diseases 2019;6:147-159.
Determining restoration levels of dystrophin is an important outcome measure of primary therapies (e.g. exon skipping (eteplirsen), stop codon readthrough (ataluren) or gene therapy). Currently there is no consensus how dystrophin could best be measured. Several different methods exist, leading to variable outcome measurements. Therefore a workshop was held to discuss the benefits and limitations of the different methods. Another important point is that the reference level of a healthy person varies between samples/labs. Therefore it was agreed that a common reference sample should be used by everyone.
Representatives of academia, patient organisations, industry and the United States Food and Drug Administration attended a workshop on dystrophin quantification methodology. The aims of the workshop were to provide an overview of methods used to quantify dystrophin levels in human skeletal muscle and their applicability to clinical trial samples, outline the gaps with regards to validating the methods for robust clinical applications prior to regulatory agency review, and to align future efforts towards further optimizing these methods. The workshop facilitated a constructive but also critical discussion on the potential and limitations of techniques currently used in the field of translational research (western blot and immunofluorescence analysis) and emerging techniques (mass spectrometry and capillary western immunoassay). Notably, all participants reported variation in dystrophin levels between muscle biopsies from different healthy individuals and agreed on the need for a common reference sample.