Pinpoint, stratifying OA patients for BMP7 peptide responsiveness and susceptibility for chondrocyte hypertrophy, followed by identifying synovial fluid biomarkers

Osteoarthritis (OA) is a progressive high-pain burdened disease with a devastating impact on quality of life for the patient. The prevalence of OA is exponentially growing and designated by the WHO as a “Priority Disease”. In the Netherlands, currently almost 1.5 million people have osteoarthritis, which will increase to 2.5 million in 2040. Currently, no OA disease-modifying treatment exists that halts the cartilage degeneration that is so typically associated with OA. A cell-type called chondrocytes exclusively populates cartilage tissue and chondrocyte hypertrophy is a pathological phenomenon that is an important driver of OA development and progression. Chondrocyte hypertrophy is associated with terminal cell differentiation (apoptosis), an inflammatory and katabolic cellular behavior, as well as calcification of the surrounding cartilage matrix. Therefore, chondrocyte hypertrophy is a pivotal target biology in the development of OA disease-modifying interventions.

The Laboratory for Experimental Orthopedics at Maastricht University has developed a proprietary chondrocyte hypertrophy-suppressing BMP7 peptide that has been licenced to Chondropeptix. This peptide has shown to inhibit chondrocyte hypertrophy and experimental OA progression in rats, including relief of pain-related behavior and inflammatory responses. This peptide is thus promising to further develop into a clinically applicable OA treatment.

Many of the historically promising OA therapies failed because of lack (or improper) patient stratification, and assuming a one-size-fits-all treatment strategy would work. Therefore, in order to safeguard and accelerate the transformation of the BMP7 peptide into a clinical therapy for OA, corresponding patient stratification strategies should be simultaneously developed.

The primary goal of this project is to obtain OA patient chondrocyte stratifying knowledge on BMP7 peptide responsiveness and chondrocyte hypertrophy stratification. Identification of matching synovial fluid biomarkers could be employed diagnostically in future clinical trials and patient care. This project will therefore serve as an essential bridge between therapeutic molecules and the OA patient population.