Repurposing the antihistamine cyproheptadine for osteoarthritis: nothing to sneeze at

Osteoarthritis (OA) is a highly prevalent and painful joint disease in desperate need of disease-modifying therapeutics. Decline in the activity of the Forkhead box O (FOXO) family of transcriptional regulators in articular chondrocytes may contribute to the development of OA. In a study in this issue of the JCI, Kurakazu et al. screened compounds for FOXO activators and discovered that the antihistamine cyproheptadine activated FOXO3 through inhibition of the histamine H1 receptor. Cyproheptadine modulated the activity of OA-relevant pathways and reduced the severity of joint damage and pain behavior in a mouse model of OA, thus showing potential for development as a disease-modifying OA drug.