Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies.

Published

Journal Article

The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na+ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.

Full Text

Duke Authors

Cited Authors

  • Bang, S; Yoo, J; Gong, X; Liu, D; Han, Q; Luo, X; Chang, W; Chen, G; Im, S-T; Kim, YH; Strong, JA; Zhang, M-Z; Zhang, J-M; Lee, S-Y; Ji, R-R

Published Date

  • February 2018

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 22 - 41

PubMed ID

  • 29333591

Pubmed Central ID

  • 29333591

Electronic International Standard Serial Number (EISSN)

  • 1995-8218

Digital Object Identifier (DOI)

  • 10.1007/s12264-018-0203-0

Language

  • eng

Conference Location

  • Singapore