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.
Neurosci Bull
; 34(1): 22-41, 2018 Feb.
Article
en En
| MEDLINE
| ID: mdl-29333591
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Canal de Sodio Activado por Voltaje NAV1.7
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Anticuerpos Monoclonales
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Neuralgia
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurosci Bull
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos