Candidates for Intra-Articular Administration Therapeutics and Therapies of Osteoarthritis

Osteoarthritis (OA) is a disease mainly characterized by cartilage degeneration, pathological changes in entire joint, such as joint capsule thickening, osteophyte formation, subchondral sclerosis, and synovitis. A prolonged low-grade inflammation is thought to play a pivotal role in OA initiation and progression. Activation of innate immunity by the decomposition products of the joint matrix generated by trauma or mechanical overload causes synovitis. Synovitis induces production of proinflammatory mediators from synovial cells, immune cells, chondrocytes, or cells in subchondral bone. Risk factors for OA, such as aging, injury history, obesity, and some genetic backgrounds are thought to trigger or prolong inflammation. Since knee OA is not a life-threatening disease, minimally invasive treatment at an outpatient level is preferred; intra-articular (IA) injections of corticosteroids and Hyaluronan are commonly employed for knee OA. Since OA progresses over a long period of time, early intervention is important so that symptoms can be controlled throughout life. The development of a disease-modifying osteoarthritis drug (DMOAD) that can be administered by IA injection, which is attracting attention as a point-of-care therapeutic, is desired. However, no DMOADs have been developed. Novel treatment options are being developed with the expectation of controlling inflammation and promoting cartilage regeneration in OA. Options include recombinant protein, gene therapy, platelet-rich plasma, and cell therapy. I will present the current status and challenges that the new biologics bring to treating OA, especially protein therapeutics, gene therapy, and nucleic-acid therapeutics.