Potential targets for the treatment of pain—— NGF

Studies have shown that NGF plays a key role in peripheral hyperalgesia and inflammation, participates in the regulation of chronic pain, and is a potential target for chronic pain treatment. NGF was first identified in nociceptive primary neuron/fiber development and was later found to play a role in inflammatory hyperalgesia in adults. Since its discovery, more and more studies have proved that NGF is involved in the occurrence of musculoskeletal pain, arthritis pain and cancer pain. NGF levels were found to be significantly elevated in pain states, including inflammatory pain and tumor-related pain, and NGF mRNA was also found to be significantly increased in the skin and muscle of some surgical incisions. Selective antagonists of NGF have been shown to be highly effective in animal models of various acute and chronic pain states without significant side effects.

Nerve growth factor (NGF) is a nerve growth factor stimulated and released by peripheral tissue injury, and its expression level is usually increased in chronic neurological diseases. NGF binds to its receptor TrkA, activates the phosphorylation of TrkA intracellular domain kinase and downstream signaling pathways, and leads to the production of neurotransmitters and ectopic discharge, resulting in the occurrence of pain. Based on the above mechanism, NGF is a potential target for pain therapy.

Studies have shown that anti-NGF antibodies can interfere with the nervous system by blocking the binding of NGF to its receptors, thereby exerting an analgesic effect. Therefore, many domestic and foreign pharmaceutical companies are developing antibody drugs against NGF for pain treatment. Tanezumab, jointly developed by Pfizer/Eli Lilly, was the first NGF antibody drug to enter the clinic, but its road to the market was blocked several times due to its safety issues. The problem encountered challenges, and the clinical trial was stopped by the FDA. Although safety issues have become the main bottleneck in the development of this target drug, as a promising next-generation analgesic drug target in the field of pain, it still cannot stop the continuous stream of latecomers. Absolute research and development enthusiasm. It is worth mentioning that last year, the U.S. FDA approved Solensia (Frunevetmab injection), an NGF monoclonal antibody drug, to control pain associated with osteoarthritis in cats. Although it is an animal drug, it is also a success of NGF monoclonal antibody. The subsequent research and development of NGF antibody drugs for human pain treatment also brought certain confidence. At present, the NGF antibodies of many domestic companies have obtained clinical approval from NMPA, including DS002 from Dashi Pharmaceutical, SMR7694 from Unnamed Biotech, EP-9001A from Urobiology, a subsidiary of Yuandong Biology, and Akeso Biotech. AK115, Technomicrobio's TNM009, etc.