Official websites use. Share sensitive information only on official, secure websites. Correspondence: emma. Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies.
All failed to show modification of disease course as dictated by the primary and secondary outcome measures selected: the myostatin inhibition story, thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models have failed to translate into clinical benefit to patients have been purported.
However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.
Keywords: myostatin inhibition, Duchenne Muscular Dystrophy, skeletal muscle, muscle development, clinical trials, translation. Therapeutic myostatin inhibition has been purported for muscular dystrophy, cachexia, sarcopenia, and disuse atrophy associated with osteoporosis, diabetes, amyotrophic lateral sclerosis and multiple sclerosis [ 3 ].
While myostatin inhibition cannot correct the primary defect in many of these diseases, severe and progressive muscle wasting could, theoretically, be attenuated, halted or reversed to increase the longevity and quality of lives of patients and reduce burden on the healthcare system. Subsequent development of a range of myostatin inhibitors and promising pre-clinical results encouraged human trials.
