Recent scientific advances, including those by Decibel Therapeutics’ founders, have provided insights into the link between hearing dysfunction and inner ear pathology, and point to new therapeutic targets to address these issues. Below are select references that support Decibel’s platform and approach to discovering and developing new medicines to protect, repair, and restore hearing.

  1. Bramhall, N., Shi, F., Arnold, K., Hochedlinger, K. and Edge, A.S.B. Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea. Stem Cell Reports 2:311-322, 2014.
  2. Fujioka, M., Tokano, H., Fujioka, K.S., Okano, H. and Edge, A.S.B. Generating mouse models of degenerative diseases using Cre/lox mediated in vivo mosaic cell ablation. J. Clin. Invest. 121:2462-2469, 2011.
  3. Gillespie, P., and Müller, U. Mechanotransduction by Hair Cells: Models, Molecules, and Mechanisms. Cell Volume 139, Issue 1, p33–44, 2 October 2009. DOI: 10.1016/j.cell.2009.09.010.
  4. Gomez-Casati, M.E., Murtie, J., Rio, C., Stankovic, K., Liberman, M.C. and Corfas, G. Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression. Proc Natl Acad Sci USA 2010 107:17005-10.
  5. Grillet, N., Xiong, W., Reynolds, A., Kazmierczak, P., Sato, T., Lillo, C., Dumont, R.A., Hintermann, E., Sczaniecka, A., Schwander, M., Williams, D., Kachar, B., Gillespie, P.G., and Müller, U. Harmonin mutations cause mechanotransduction defects in cochlear hair cells. Neuron. 2009 May 14;62(3):375-87. doi: 10.1016/j.neuron.2009.04.006.
  6. Hedstrom, K.L., Murtie, J.C., Albers, K.M., Calcutt, N. and Corfas, G. Treating small fiber neuropathy by topical application of a small molecule modulator of ligand-induced GFRα/RET receptor signaling. PNAS 2014 Feb 11;111(6):2325-30.
  7. Kujawa, S.G., and Liberman, M.C. Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss. Hearing Research (2015). doi:10.1016/j.heares.2015.02.009
  8. Makary, C.A., Shin, J., Kujawa, S.G., Liberman, M.C., and Merchant, S.N. Age-Related Primary Cochlear Neuronal Degeneration in Human Temporal Bones. Journal of the Association for Research in Otolarynology 12: 711–717 (2011). DOI: 10.1007/s10162-011-0283-2.
  9. Makinodan, M., Rosen, K.M., Ito, S., and Corfas, G. A critical period for experience-dependent myelination of the prefrontal cortex. Science 2012 337:1357-1360.
  10. Martinez-Monedero, R., Corrales, C.E., Cuajungco, M.P., Heller, S., Edge, A.S. Reinnervation of hair cells by auditory neurons after selective removal of spiral ganglion neurons. J Neurobiol. 2006 Mar;66(4):319-31.
  11. Martinez-Monedero, R., Yi, E., Oshima, K., Glowatzki, E., and Edge, A.S. Differentiation of inner ear stem cells to functional sensory neurons. Dev Neurobiol. 2008 Apr;68(5):669-84. doi: 10.1002/dneu.20616.
  12. Mellado Lagarde, M.M., Wan, G., Zhang, L., Gigliello, A.R., McInnis, J.J., Zhang, Y., Bergles, D., Zuo, J., Corfas, G. Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16919-24.‎
  13. Mizutari, K., Fujioka, M., Hosoya, M., Bramhall, N., Okano, H.J., Okano, H. and Edge, A.S.B. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron 77:58-69, 2013.
  14. Müller, U., and Gillespie, P. New treatment options for hearing loss. Nature Reviews Drug Discovery 14, 346–365 (2015). doi:10.1038/nrd4533. Published online 20 March 2015.
  15. Sergeyenko, Y., Lall, K., Liberman, M.C., and Kujawa, S.G. Age-Related Cochlear Synaptopathy: An Early-Onset Contributor to Auditory Functional Decline. The Journal of Neuroscience, August 21, 2013. 33(34):13686 –13694.
  16. Shi, F., Hu, L., Jacques, B., Mulvaney, J.F., Dabdoub, A., and Edge, A.S.B. b-catenin is required for hair cell differentiation in the cochlea. J Neurosci, 34:6470-6479, 2014.
  17. Shi, F., Hu, L. and Edge, A.S.B. Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors. Proc, Natl. Acad. Sci. 110:13851-13856, 2013.
  18. Shi, F., Kempfle, J. and Edge, A.S.B. Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea. J. Neurosci. 32:9639-9648, 2012.
  19. Siemens, J., Lillo, C., Dumont, R.A., Williams, D., Gillespie, P.G., and Müller. U. CDH23 is a component of the tip link in hair cell stereocilia. Nature 428, 950-955, 29 April 2004. doi:10.1038/nature02483. Published online 31 March 2004.
  20. Viana, L.M., O’Malley, J.T., Burgess, B.J., Jones, D.D., Oliveira, C.A.C.P., Santos, F., Merchant, S.N., Liberman, L.D., and Liberman, M.C. Cochlear neuropathy in human presbycusis: confocal analysis of hidden hearing loss in post-mortem tissue. Hearing Research 2015 Sep;327:78-88. doi: 10.1016/j.heares.2015.04.014. Epub 2015 May 19.
  21. Wan, G., Gómez-Casati, M.E., Gigliello, A.R., Liberman, M.C., Corfas, G. Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma. Elife. 2014 Oct 20;3. doi: 10.7554/eLife.03564.
  22. Xiong, W., Grillet, N., Elledge, H., Wagner, T.F.J., Zhao, B., Johnson, K.R., Kazmierczak, P., and Müller, U. TMHS is an Integral Component of the Mechanotransduction Machienry of Cochlear Hair Cells. Cell. 2012 Dec 7;151(6):1283-95. doi: 10.1016/j.cell.2012.10.041.
  23. Zhao, B., Wu, Z., Grillet, N., Yan, L., Xiong. W., Harkins-Perry, S., and Müller, U. TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells. Neuron. 2014 Dec 3;84(5):954-67. doi: 10.1016/j.neuron.2014.10.041. Epub 2014 Nov 20.
  24. Zilberstein, Y., Liberman, M.C. and Corfas, G. Inner Hair Cells are not required for survival of spiral ganglion neurons in the adult cochlea. J. Neurosci. 2012 32:405-410.