Neurology

Cell culture, worm and mouse studies suggest inhibiting HDAC6 and other HDACs could help treat Cockayne syndrome, a leukodystrophy caused by ERCC6 mutations that is associated with defects in autophagy, neurogenesis and neuronal differentiation. In a patient-derived fibroblast cell line, an HDAC6 inhibitor tool compound or the HDAC inhibitor Zolinza vorinostat decreased levels of impaired autophagy markers compared with vehicle. In a Caenorhabditis elegans model of Cockayne syndrome, Zolinza decreased levels of impaired autophagy markers compared with vehicle. In a mouse model of the disease, Zolinza decreased subcutaneous fat loss, epidermal hyperplasia, fibrosis, inflammation and levels of impaired autophagy markers in the skin. Next steps could include testing whether HDAC inhibitors could improve neurological symptoms in mouse models of Cockayne syndrome...