Project in detail: Development of a new treatment for osteoarthritis
Osteoarthritis (OA) is associated with significant pain and functional impairment that can severely limit mobility and quality of life and as such, is a significant global healthcare burden that is increasing with the aging population. Despite the high prevalence of OA, there are still no effective treatments that can limit progression of disease or increase the function of affected joints. Osteoarthritis is a whole joint disease, with a complex pathogenesis leading to structural destruction and failure of the synovial joint. The hallmarks of OA are destruction of the articular cartilage matrix and underlying subchondral bone. It is well established that this destruction is driven by the cells of the articular cartilage (chondrocytes) which adopt an abnormal hypertrophic phenotype. Several types of molecule including cytokines, enzymes and transcription factors maintain homeostasis of healthy cartilage.
We have previously shown that matrix extracellular phosphoglycoprotein (MEPE) is an important regulator of cartilage homeostasis and chondrocyte hypertrophy. Importantly, we have also demonstrated that MEPE levels are lower in mice predisposed to age-related OA. Peptides derived from MEPE were shown to increase articular cartilage formation and are being tested in patients with mild to moderate patello-femoral OA in two phase II clinical trials.
This project will investigate the use of MEPE and MEPE-derived peptides as therapies for OA using our novel drug delivery system, known as the latency-associated peptide (‘LAP’) fusion protein technology. This approach enables the delivery of high local concentrations of therapeutic molecules at site(s) of disease, thus eliminating side-effects and increasing therapeutic efficacy. Efficient delivery of MEPE and MEPE-derived peptides to arthritic joints in vivo will allow us to test the efficacy of these proteins on the pathologic changes that occur to bone and cartilage in age-related joint disease.
The student will engage in a novel translational area of research that may contribute to the development of novel therapies for age-related arthritic disease. This interdisciplinary project will provide diverse training including: engineering of recombinant proteins, expression of recombinant proteins from mammalian tissue culture systems, protein biochemistry techniques, methods in molecular biology and harvesting of ex vivo tissue. Additional training in scientific writing, science communication, project management and teamwork will be provided formally through postdoctoral training programmes at the University of Brighton and Brighton and Sussex Medical School which is a partnership between the Universities of Brighton and Sussex.