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

Publication ,  Journal Article
Lee, J-H; Park, C-K; Chen, G; Han, Q; Xie, R-G; Liu, T; Ji, R-R; Lee, S-Y
Published in: Cell
June 5, 2014

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.

Duke Scholars

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

June 5, 2014

Volume

157

Issue

6

Start / End Page

1393 / 1404

Location

United States

Related Subject Headings

  • Voltage-Gated Sodium Channel Blockers
  • Synaptic Transmission
  • Spinal Cord
  • Sequence Alignment
  • Pruritus
  • Pain
  • Neurons
  • NAV1.7 Voltage-Gated Sodium Channel
  • Molecular Sequence Data
  • Models, Molecular
 

Citation

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Lee, J.-H., Park, C.-K., Chen, G., Han, Q., Xie, R.-G., Liu, T., … Lee, S.-Y. (2014). A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief. Cell, 157(6), 1393–1404. https://doi.org/10.1016/j.cell.2014.03.064
Lee, Jun-Ho, Chul-Kyu Park, Gang Chen, Qingjian Han, Rou-Gang Xie, Tong Liu, Ru-Rong Ji, and Seok-Yong Lee. “A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief.Cell 157, no. 6 (June 5, 2014): 1393–1404. https://doi.org/10.1016/j.cell.2014.03.064.
Lee J-H, Park C-K, Chen G, Han Q, Xie R-G, Liu T, et al. A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief. Cell. 2014 Jun 5;157(6):1393–404.
Lee, Jun-Ho, et al. “A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief.Cell, vol. 157, no. 6, June 2014, pp. 1393–404. Pubmed, doi:10.1016/j.cell.2014.03.064.
Lee J-H, Park C-K, Chen G, Han Q, Xie R-G, Liu T, Ji R-R, Lee S-Y. A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief. Cell. 2014 Jun 5;157(6):1393–1404.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

June 5, 2014

Volume

157

Issue

6

Start / End Page

1393 / 1404

Location

United States

Related Subject Headings

  • Voltage-Gated Sodium Channel Blockers
  • Synaptic Transmission
  • Spinal Cord
  • Sequence Alignment
  • Pruritus
  • Pain
  • Neurons
  • NAV1.7 Voltage-Gated Sodium Channel
  • Molecular Sequence Data
  • Models, Molecular