INHIBITION OF WINGLESS-RELATED INTEGRATION SITE (WNT) SIGNALLING MAY TREAT OSTEOARTHRITIS OF THE KNEE.

Osteoarthritis (OA) of the knee is the leading cause of disability in individuals over 60 years of age. Currently, treatments have been limited to analgesic and anti-inflammatory medications that reduce pain and improve function for short periods of time, until a joint replacement is required. Recently, inhibition of the Wnt/beta-catenin signaling pathway with lorecivivint (LOR; SMO496) was found to prevent the deterioration of the cartilage in preclinical models of posttraumatic OA. LOR appears to reduce both STAT signaling and Wnt signaling in the chondrocyte, allowing for both a reduction in pain and the production of enzymes associated with cartilage destruction. LOR has been tested in both Phase I and Phase 2 trials, and a dose of 0.07ug/kg administered through intra-articular injection reduced pain and preserved the articular joint space as assessed by radiograph. Therefore, reduction in Wnt signaling in the knee joint may reduce signs and symptoms and alter the course of osteoarthritis.