Zagociguat prevented stressor-induced neuromuscular dysfunction, improved mitochondrial physiology, and increased exercise capacity in diverse mitochondrial respiratory chain disease zebrafish models.

Preclinical evaluation of zag demonstrated its safety, significant protection of neuromuscular dysfunction and/or acute RC stressor-induced decompensation, and improved mitochondrial physiology across multiple different genetic and/or pharmacologic models of RC-deficient PMD. Thus, zag may yield therapeutic potential for an array of diseases with mitochondrial dysfunction beyond MELAS, potentially including Leigh syndrome spectrum disorder and primary mitochondrial myopathies.