The pattern of dystrophin protein expression is heterogeneous in patients with Becker muscular dystrophy (BMD), according to a study published in the Journal of Neuropathology and Experimental Neurology. This finding will help better assess dystrophin restoration therapies, according to Silvia Torelli, BS, and the coauthors of the study.
The dystrophin expression pattern is variable among patients with dystrophinopathy and researchers have been using new techniques to quantify dystrophin expression in the muscles of children with Duchenne muscular dystrophy (DMD). A team of researchers led by Francesco Muntoni, MD, described the expression pattern of dystrophin in patients with DMD, BMD, and intermediate DMD/BMD using Western blotting and an automated image analysis platform.
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The results showed a significant correlation between Western blot and immunofluorescent quantification which indicated uniformity between the different methods. However, there was significant heterogeneity between diseases and even within the same disease in terms of dystrophin expression. This was irrespective of the amount of signal detected on the blot because of the variability in the intensity of the fluorescence and the sarcolemmal circumference coverage of dystrophin.
“To benchmark the success of the therapeutic intervention, a clear understanding of dystrophin expression patterns in dystrophinopathy patients is vital,” the researchers wrote. They added “Improved understanding of the heterogeneity of dystrophin expression in BMD, [intermediate clinical phenotypes], and DMD patients will be vital to investigators who use muscle pathology to benchmark outcomes in future DMD clinic trials.”
DMD is caused by out-of-frame mutations in the DMD gene leading to no functional dystrophin protein being produced by cells, while BMD is milder due to in-frame deletions in the gene. This results in the production of a shorter but still functional dystrophin protein.
Torelli S, Scaglioni D, Sardone V, et al. High-throughput digital image analysis reveals distinct patterns of dystrophin expression in dystrophinopathy patients. J Neuropathol Exp Neurol. Published online September 8, 2021. doi:10.1093/jnen/nlab088