A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief

• Published in: Cell 2014-06, Vol.157 (6), p.1393-1404
• Main Authors: Lee, Jun-Ho, Park, Chul-Kyu, Chen, Gang, Han, Qingjian, Xie, Rou-Gang, Liu, Tong, Ji, Ru-Rong, Lee, Seok-Yong
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - therapeutic use; HEK293 Cells; Humans; Inflammation - chemically induced; Inflammation - pathology; Mice; Models, Molecular; Molecular Sequence Data; NAV1.7 Voltage-Gated Sodium Channel - chemistry; NAV1.7 Voltage-Gated Sodium Channel - metabolism; Neurons - metabolism; Pain - drug therapy; Pruritus - drug therapy; Sequence Alignment; Spinal Cord - metabolism; Synaptic Transmission - drug effects; Voltage-Gated Sodium Channel Blockers - therapeutic use
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2014.03.064

Voltage-gated sodium (NaV) channels control the upstroke of the action potentials in excitable cells. Multiple studies have shown distinct roles of NaV channel subtypes in human physiology and diseases, but subtype-specific therapeutics are lacking and the current efforts have been limited to small molecules. Here, we present a monoclonal antibody that targets the voltage-sensor paddle of NaV1.7, the subtype critical for pain sensation. This antibody not only inhibits NaV1.7 with high selectivity, but also effectively suppresses inflammatory and neuropathic pain in mice. Interestingly, the antibody inhibits acute and chronic itch despite well-documented differences in pain and itch modulation. Using this antibody, we discovered that NaV1.7 plays a key role in spinal cord nociceptive and pruriceptive synaptic transmission. Our studies reveal that NaV1.7 is a target for itch management, and the antibody has therapeutic potential for suppressing pain and itch. Our antibody strategy may have broad applications for voltage-gated cation channels.