Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker
Running title: Inhibition of pain and cough by BW-031
Ivan Tochitsky1*, Sooyeon Jo2*, Nick Andrews1, Masakazu Kotoda1, Benjamin Doyle1, Jaehoon Shim1, Sebastien Talbot1,3, David Roberson1, Jinbo Lee4, Louise Haste5, Stephen M. Jordan5, Bruce D. Levy6#, Bruce P. Bean2#, Clifford J. Woolf1,2#
1 F.M. Kirby Neurobiology Research Center, Boston Children’s Hospital, Boston, MA 02115
2 Department of Neurobiology, Harvard Medical School, Boston MA 02115
3 Départément de Pharmacologie et Physiologie, Université de Montréal, Canada
4 Sage Partner International, Andover MA 01810
5 Covance Inc., Woolley Rd, Alconbury, Huntingdon PE28 4HS, United Kingdom
6 Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
* These authors contributed equally: Ivan Tochitsky, Sooyeon Jo.
#Co-senior authors
Correspondence to B.D.L., B.P.B. and C.J.W.
Bruce Bean ORCID ID: 0000-0002-5093-3576
Word count: 2,861
Data Availability Statement: The data that support the findings of this study are available from the corresponding authors upon reasonable request.
Acknowledgements
We are grateful to Alyssa Grantham, Mary Kate Dornon, Yu Wang, Daniel Taub, Huan Wang and Lee Barrett for technical assistance, to the Boston Children’s Hospital PK-lab for assistance with LC/MS experiments, and to Ronald Blackman, James Ellis, and Richard Batycky for helpful discussions and suggestions. This work was supported by the National Institutes of Health National Institute of Neurological Diseases and Stroke [R35NS105076 (C.J.W.), R01NS036855 (B.P.B.), R01NS110860 (B.P.B.), R01HL122531 (B.D.L.)], the Department of Defense [W81XWH-15-1-0480 (C.J.W. & B.B.)], Boston Biomedical Innovation Center, the Blavatnik Biomedical Accelerator Fund, and the Boston Children’s Hospital’s Technology Development Fund.
Author Contributions
I.T., S.J., N.A., M.K., B.D.L., B.P.B. and C.J.W. designed experiments; I.T., S.J., N.A., M.K., B.D., J.S., S.T., D.R., J.L., L.H., S.M.J. carried out experiments; I.T., S.J., N.A., M.K., B.D., J.S., L.H. and S.M.J. analyzed data; I.T., S.J., N.A., M.K., B.D., J.S., B.D.L., B.P.B. and C.J.W. provided advice on the interpretation of data; I.T., B.D.L, B.P.B and C.J.W. wrote the manuscript with input from all co-authors; B.D.L., B.P.B., and C.J.W. supervised the study. All authors approved the final manuscript.
Conflict of Interest
B.D.L., B.P.B. and C.J.W. are cofounders of and equity holders in Nocion Therapeutics which is developing charged sodium channel blockers as treatments for various disease indications, including cough, and which has licensed BW-031 from Harvard Medical School. I.T., S.J., N.A., S.T. and D.R. also have founder shares in Nocion.