Effects of Dantrolene Therapy on Disease Phenotype in Dystrophin Deficient mdx Mice

In this study we demonstrated that Dantrolene treatment has no significant beneficial effects at the tested dose in young mdx mice. Dantrolene failed to improve the muscle phenotype as measured by functional, behavioral, histological, and imaging assays. The exception being CK levels, which were significantly decreased by Dantrolene treatment. Dantrolene is a known muscle relaxant and used for the treatment of malignant hyperthermia 11. It decreases the calcium released in skeletal muscle upon stimulation, resulting in decreased muscle contraction 19. In fact, functional assessments such as grip strength and open field activity were decreased in Dantrolene-treated mice compared to their vehicle-treated counterparts. This is likely a result of the muscle relaxant properties of the drug. This further indicates that the treatment does not improve muscle function or strength. To minimize variation in the functional and behavioral assays, only female mice were used because there are clear gender differences in mdx muscle pathology between sexes 21 and to reduce variability others and we have suggested that pre-clinical tests should be performed on groups of mdx mice of the same sex 22. It is clear from the results that Dantrolene did not reduce inflammation in mdx mice. Cathepsin B activity (macrophage/muscle) as measured by optical imaging is unaltered in the two mdx mouse groups. These findings were confirmed by analysis of H&E sections that also indicate no change in the hi...
Source: PLOS Currents Muscular Dystrophy - Category: Neurology Authors: Source Type: research