Arthritis presently impacts more than fifty million adults, plaguing one in five Americans with the number one cause of disability in the U.S. Examples of current treatments against arthritis include intra-articular injections of hyaluronic acid or corticosteroids, but these treatments are limited to providing short term pain relief despite being expensive and requiring frequent injections. There are currently no disease-modifying osteoarthritis (OA) drugs, as MMP inhibition and senescent cell removal have garnered no significant difference between treatment and placebo, and inflammatory cytokine (IL-1) inhibition (anakinra) was ineffective in preventing joint pain or cartilage degradation. Additionally, tanezumab non-opioid treatment failed owing to risks of rapidly progressive osteoarthritis that may necessitate a total joint replacement. Injuries such as ACL tears increase Piezo1 expression in murine chondrocytes as well as mechano-vulnerability and can thereby induce post-traumatic OA, for which there is also no true cure.
The university has identified a new application of GsMTx4-D peptide (originally developed by TONUS for use in clinical trials of Duchenne Musculo dystrophy disease) for joint-injury-induced osteoarthritis (OA). While several chondrocyte-targeting candidate drugs in OA failed due to inefficient delivery over the cartilage matrix, our new GsMTx4D-conjugates are designed to specifically deliver to the articular cartilage.
GsMTx4 treatment post-ACL-I improved joint integrity indicated by reduced cartilage erosion with intact articular cartilage thickness and by reduced nerve innervation in the knee. GsMTx4-treatment suppressed mechano-vulnerability of chondrocytes (reduced cellular death by impact), and recovered gait parameters. Thus, this therapy significantly reduced OA progression by decreasing the degree of cartilage degeneration and joint pain.