The development of osteoarthritis (OA) in joints is a complex interplay between joint tissues and katabolic molecules, progressively leading to the destruction of functional joint cartilage causing chronic pain and immobility. OA is treated symptomatically, with the ultimate treatment option being total joint replacement. The increasingly ageing population is in need of effective disease-modifying osteoarthritic drugs to slow down disease progression and ultimately avoid total joint replacement.
Healthy cartilage is maintained by chondrocytes that produce cartilage matrix important for unencumbered joint function. Development of osteoarthritis is a progressive slow process in which chondrocytes become dysregulated because molecular gate keepers fail to provide ample protection against developing pathological chondrocyte hypertrophic changes. Reversing the dysregulated chondrocyte to a normal healthy status is expected to provide a powerful means to protect articular cartilage from degeneration in OA (1).
Bone morphogenetic protein 7 (BMP7) is a natural anabolic growth factor for articular cartilage homeostasis(2) , but its abundancy in cartilage declines with increasing OA-related cartilage degeneration(3). BMP7 maintains the chondrocyte normal health status by preventing chondrocyte hypertrophic differentiation by restoration of chondrocyte NKX3.2 expression, one of the molecular gate keepers for normal articular chondrocyte function(4).
Chondropeptix’s team discovered that a small BMP7-derived peptide has therapeutically advantageous BMP7 bioactivity for chondrocytes. The BMP7 peptide normalizes dysregulated chondrocytes from OA patients to a normal healthy state in vitro. Extensive in vitro characterization of the core peptide bioactivity on human articular chondrocytes has demonstrated its OA disease-modifying potential(5).
Based on the core BMP7 peptide sequence, Chondropeptix is now developing the lead compound CPX-101.
1. Ripmeester et al., 2018. Frontiers in Bioengineering and Biotechnology
2. Abula et al., 2015. FEBS Letters
3. Merrihew et al., 2003. Journal of Orthopaedic Research
4. Caron et al., 2015. Arthritis and Rheumatology
5. Caron et al., 2018. Osteoarthritis and Cartilage (conference abstract)