TARGETTING JOINT PAIN BY INTRA-ARTICULAR INJECTION OF DRUG DEPOTS RELEASING NGF NEUTRALIZING ANTIBODY FRAGMENTS

Purpose: Osteoarthritis is a debilitating disease affecting a growing number of patients worldwide. It leads to progressive loss of cartilage, results in pain and loss of function. This obstructive pain response is the main reason for searching medical help and eventually choosing for joint replacement surgery. However, in many situations, especially in young patients, it is desirable to postpone joint replacement surgery as long as possible. Therefore, extensive research has been performed on new analgesics for treating OA joint pain. One promising approach is to block nerve growth factor (NGF) using the variable domain of heavy chain only antibodies (VHH). While strong pain reduction can be achieved, the systemic blocking of NGF is expensive, results in over treatment, and leads to unwanted side effects and an unfavorable risk/benefit ratio. Moreover, fine tuning of blocking extreme pain, while keeping a physiologically relevant pain signal function is difficult. Targeted treatment with small, easy to produce and low cost VHH nanobodies could potentially be a solution for these problems. Here, we propose a new strategy to block NGF signaling by an intra-articular injection of a drug depot resulting in the sustained release of anti-NGF VHH antibodies in the affected joints. This can enable sustained pain relief, locally in the osteoarthritic joint while minimizing the risk of systemic side effects.