RETRACTED: A Monoclonal Antibody that Targets a NaV1.7 Channel Voltage Sensor for Pain and Itch Relief
Authors: Seok-Yong Lee
Qingjian Han
Jun-Ho Lee
Ru-Rong Ji
Rou-Gang Xie
Tong Liu
Chul-Kyu Park
Gang Chen
Journal: Cell (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Voltage-gated sodium channels; NaV channel subtypes; monoclonal antibody; NaV1.7; pain sensation
Affiliations: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA., Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA., Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: ., Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: .

Abstract:  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. 

Retracted: Yes

PubPeer comments:
 Retraction Notice to: A Monoclonal Antibody that Targets a NaV1.7 Channel Voltage Sensor for Pain and Itch Relief JUNE 25, 2020 In this publication, using in vitro and in vivo approaches, we described and characterized a monoclonal antibody (mAb) that binds to the voltage sensor of the sodium channel subtype Nav1.7 and inhibits channel function. A follow-up study by Liu et al. reported that a similar but distinct recombinant mAb targeting Nav1.7 did not show significant in vitro activities (Liu et al., 2016, F1000 Res. 5, 2764, https: doi.org 10.12688 f1000research.9918.1), which prompted us to re-examine our previous results. In the process, we found irregularities in some of the raw data used for the published in vitro results, and we notified our institution, Duke University, about the irregularities. The institution subsequently appointed an ad hoc committee that concluded that the first author, Jun-Ho Lee, fabricated and or falsified the results in Figures 3A, 3C, 3D, and 4. While subsequent work has both clarified the distinct in vitro activities of the two antibodies and confirmed the in vivo activity of our antibody (Bang et al., 2018, Neurosci. Bull. 34, 22u201341, https: doi.org 10.1007 s12264-018-0203-0), we feel that the responsible course of action is to retract our paper because it contains falsified data. We sincerely apologize to the scientific community for the inconvenience and confusion that we have caused. The first author, Jun-Ho Lee, did not respond to the request to sign this retraction. DOI: https: doi.org 10.1016 j.cell.2020.06.019 ,