A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss
Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss receive...
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| Published in: | Nature communications Vol. 15; no. 1; pp. 1896 - 9 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Nature Publishing Group UK
01.03.2024
Nature Publishing Group Nature Portfolio |
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| ISSN: | 2041-1723, 2041-1723 |
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| Abstract | Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (
N
= 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (
N
= 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63;
P
= 0.252 and −0.46 dB; 95% CI −1.94 to 1.03;
P
= 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met.
Pharmacological inhibition of gamma-secretase induced partial recovery of hearing in animal models. Here, the authors present the safety and efficacy results and key learnings of the First in Human Phase I/IIa study of a gamma-secretase inhibitor in patients with acquired Hearing Loss. |
|---|---|
| AbstractList | Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met. Abstract Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63; P = 0.252 and −0.46 dB; 95% CI −1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met. Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I ( N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa ( N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63; P = 0.252 and −0.46 dB; 95% CI −1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met. Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met. Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63; P = 0.252 and −0.46 dB; 95% CI −1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met.Pharmacological inhibition of gamma-secretase induced partial recovery of hearing in animal models. Here, the authors present the safety and efficacy results and key learnings of the First in Human Phase I/IIa study of a gamma-secretase inhibitor in patients with acquired Hearing Loss. Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I ( N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa ( N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63; P = 0.252 and −0.46 dB; 95% CI −1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met. Pharmacological inhibition of gamma-secretase induced partial recovery of hearing in animal models. Here, the authors present the safety and efficacy results and key learnings of the First in Human Phase I/IIa study of a gamma-secretase inhibitor in patients with acquired Hearing Loss. |
| ArticleNumber | 1896 |
| Author | Bibas, Athanasios G. Schilder, Anne G. M. Wolpert, Stephan Edge, Albert S. B. Blackshaw, Helen Pastiadis, Kostas Middelink, Leonie M. Saeed, Shakeel |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38429256$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1038_s41467_025_63053_6 crossref_primary_10_1002_advs_202509960 crossref_primary_10_1080_1061186X_2024_2349111 crossref_primary_10_1007_s00431_025_06426_9 crossref_primary_10_1080_17460751_2024_2437281 crossref_primary_10_1016_j_heares_2025_109256 crossref_primary_10_1002_advs_202410568 crossref_primary_10_1088_1758_5090_add210 crossref_primary_10_1007_s40291_024_00759_1 crossref_primary_10_1186_s40001_025_02771_5 crossref_primary_10_1002_advs_202412158 crossref_primary_10_1039_D5NH00520E crossref_primary_10_5604_01_3001_0054_5439 crossref_primary_10_1016_j_heares_2025_109328 crossref_primary_10_1371_journal_pone_0331661 crossref_primary_10_1007_s00335_025_10126_y crossref_primary_10_1097_AUD_0000000000001696 crossref_primary_10_1073_pnas_2410829122 |
| Cites_doi | 10.3389/fnins.2017.00157 10.1016/j.heares.2019.07.003 10.1097/MAO.0000000000001427 10.1080/14992027.2020.1773550 10.1523/JNEUROSCI.6366-10.2011 10.1007/s12070-014-0721-7 10.1121/1.4982923 10.1016/j.neuron.2012.10.032 10.3109/01050398609045954 10.1159/000241892 10.1016/S0140-6736(17)31073-5 10.1016/bs.pmch.2022.05.001 10.1080/14992027.2019.1638526 10.1097/MAO.0000000000002194 10.1056/NEJMra1616601 10.1152/jn.1978.41.2.365 10.3109/14992027.2013.769066 10.1097/MAO.0000000000003120 10.1523/JNEUROSCI.0937-20.2020 10.1200/EDBK_319783 10.1097/MAO.0000000000000466 10.3389/fcell.2021.710159 10.1016/j.drudis.2021.11.009 10.1016/j.ymthe.2018.03.004 10.1016/j.heares.2020.107922 10.1097/MAO.0000000000001135 |
| ContentType | Journal Article |
| Contributor | Arram, Elizabeth Yildirim, Omursen Middelink, Leonie Edge, Albert Cooper, Hannah Bilhet, Asger van Diggelen, Femke Iliadou, Eleftheria Markatos, Nikos Wilke, August Dalhoff, Ernst Vardonikolaki, Katerina Hojgaard, Karin Schade-Mann, Thore Bibas, Athanasios Schilder, Anne Kikidis, Dimitris Khalil, Sherif Schneider, Fritz van Es, Helmuth Mueller, Marcus Lowenheim, Hubert Rutten, Rolf Jan |
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| DOI | 10.1038/s41467-024-45784-0 |
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| References | Dallos, Harris (CR17) 1978; 41 Doosti, Lotfi, Moosavi, Bakhshi, Talasaz (CR21) 2014; 66 Spyridakou, Rosen, Dritsakis, Bamiou (CR28) 2020; 59 Schilder (CR8) 2019; 40 Erni (CR16) 2021; 9 CR12 Suckfuell (CR29) 2014; 35 CR31 McCormack, Fortnum (CR6) 2013; 52 McLean (CR20) 2021; 42 Zelle, Lorenz, Thiericke, Gummer, Dalhoff (CR22) 2017; 141 CR30 Hoben, Easow, Pevzner, Parker (CR18) 2017; 11 Cousins (CR11) 2022; 61 Du (CR15) 2018; 26 Hunter (CR19) 2020; 397 Wu, O’Malley, de Gruttola, Liberman (CR4) 2020; 40 Cunningham, Tucci (CR3) 2017; 377 McAlpine, Goldman, Schilder (CR23) 2022; 4 Wilson, Tucci, Merson, O’Donoghue (CR1) 2017; 390 Jerlvall, Arlinger (CR26) 1986; 15 CR2 Dillon, Day, Bant, Munro (CR5) 2020; 59 Mizutari (CR14) 2013; 77 Crowson, Hertzano, Tucci (CR7) 2017; 38 Jeon, Fujioka, Kim, Edge (CR13) 2011; 31 CR27 Kurzrock (CR24) 2021; 41 Salt, Plontke (CR25) 2009; 14 Isherwood, Gonçalves, Cousins, Holme (CR10) 2022; 27 Schilder (CR9) 2019; 380 ST Erni (45784_CR16) 2021; 9 L Jerlvall (45784_CR26) 1986; 15 H Dillon (45784_CR5) 2020; 59 PZ Wu (45784_CR4) 2020; 40 R Cousins (45784_CR11) 2022; 61 MG Crowson (45784_CR7) 2017; 38 AGM Schilder (45784_CR8) 2019; 40 A Doosti (45784_CR21) 2014; 66 C Spyridakou (45784_CR28) 2020; 59 BS Wilson (45784_CR1) 2017; 390 LL Hunter (45784_CR19) 2020; 397 LL Cunningham (45784_CR3) 2017; 377 R Kurzrock (45784_CR24) 2021; 41 X Du (45784_CR15) 2018; 26 K Mizutari (45784_CR14) 2013; 77 B Isherwood (45784_CR10) 2022; 27 45784_CR2 AN Salt (45784_CR25) 2009; 14 45784_CR27 A McCormack (45784_CR6) 2013; 52 45784_CR30 45784_CR31 45784_CR12 WJ McLean (45784_CR20) 2021; 42 M Suckfuell (45784_CR29) 2014; 35 SJ Jeon (45784_CR13) 2011; 31 AGM Schilder (45784_CR9) 2019; 380 P Dallos (45784_CR17) 1978; 41 R Hoben (45784_CR18) 2017; 11 D McAlpine (45784_CR23) 2022; 4 D Zelle (45784_CR22) 2017; 141 |
| References_xml | – volume: 11 start-page: 157 year: 2017 ident: CR18 article-title: Outer hair cell and auditory nerve function in speech recognition in quiet and in background noise publication-title: Front. Neurosci. doi: 10.3389/fnins.2017.00157 – volume: 380 start-page: 175 year: 2019 end-page: 186 ident: CR9 article-title: Early phase trials of novel hearing therapeutics: avenues and opportunities publication-title: Hear Res doi: 10.1016/j.heares.2019.07.003 – volume: 38 start-page: 792 year: 2017 end-page: 803 ident: CR7 article-title: Emerging therapies for sensorineural hearing loss publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000001427 – ident: CR2 – volume: 59 start-page: 567 year: 2020 end-page: 573 ident: CR5 article-title: Adoption, use and non-use of hearing aids: a robust estimate based on Welsh national survey statistics publication-title: Int J. Audio. doi: 10.1080/14992027.2020.1773550 – volume: 31 start-page: 8351 year: 2011 end-page: 8358 ident: CR13 article-title: Notch signaling alters sensory or neuronal cell fate specification of inner ear stem cells publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.6366-10.2011 – ident: CR12 – volume: 66 start-page: 325 year: 2014 end-page: 329 ident: CR21 article-title: Distortion Product Otoacoustic Emission (DPOAE) as an appropriate tool in assessment of otoprotective effects of antioxidants in noise-induced hearing loss (NIHL) publication-title: Indian J. Otolaryngol. Head. Neck Surg. doi: 10.1007/s12070-014-0721-7 – volume: 141 start-page: 3203 year: 2017 ident: CR22 article-title: Input-output functions of the nonlinear-distortion component of distortion-product otoacoustic emissions in normal and hearing-impaired human ears publication-title: J. Acoust. Soc. Am. doi: 10.1121/1.4982923 – ident: CR30 – volume: 77 start-page: 58 year: 2013 end-page: 69 ident: CR14 article-title: Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma publication-title: Neuron doi: 10.1016/j.neuron.2012.10.032 – volume: 15 start-page: 51 year: 1986 end-page: 56 ident: CR26 article-title: A comparison of 2-dB and 5-dB step size in pure-tone audiometry publication-title: Scand. Audio. doi: 10.3109/01050398609045954 – volume: 14 start-page: 350 year: 2009 end-page: 360 ident: CR25 article-title: Principles of local drug delivery to the inner ear publication-title: Audio. Neurootol. doi: 10.1159/000241892 – volume: 4 start-page: 33 year: 2022 end-page: 34 ident: CR23 article-title: Mind the gap—developing a sustainable pipeline for hearing therapeutics publication-title: ENT Audioloy N. – volume: 390 start-page: 2503 year: 2017 end-page: 2515 ident: CR1 article-title: Global hearing health care: new findings and perspectives publication-title: Lancet doi: 10.1016/S0140-6736(17)31073-5 – ident: CR27 – volume: 61 start-page: 1 year: 2022 end-page: 91 ident: CR11 article-title: Hearing loss drug discovery and medicinal chemistry: current status, challenges, and opportunities publication-title: Prog. Med Chem. doi: 10.1016/bs.pmch.2022.05.001 – volume: 59 start-page: 33 year: 2020 end-page: 38 ident: CR28 article-title: Adult normative data for the speech in babble (SiB) test publication-title: Int J. Audio. doi: 10.1080/14992027.2019.1638526 – volume: 40 start-page: 559 year: 2019 end-page: 570 ident: CR8 article-title: Hearing protection, restoration, and regeneration: an overview of emerging therapeutics for inner ear and central hearing disorders publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000002194 – volume: 377 start-page: 2465 year: 2017 end-page: 2473 ident: CR3 article-title: Hearing Loss in Adults publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1616601 – volume: 41 start-page: 365 year: 1978 end-page: 383 ident: CR17 article-title: Properties of auditory nerve responses in absence of outer hair cells publication-title: J. Neurophysiol. doi: 10.1152/jn.1978.41.2.365 – volume: 52 start-page: 360 year: 2013 end-page: 368 ident: CR6 article-title: Why do people fitted with hearing aids not wear them? publication-title: Int J. Audio. doi: 10.3109/14992027.2013.769066 – volume: 42 start-page: e849 year: 2021 end-page: e857 ident: CR20 article-title: Improved speech intelligibility in subjects with stable sensorineural hearing loss following intratympanic dosing of FX-322 in a phase 1b study publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000003120 – volume: 40 start-page: 6357 year: 2020 end-page: 6366 ident: CR4 article-title: Age-related hearing loss is dominated by damage to inner ear sensory cells, not the cellular battery that powers them publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.0937-20.2020 – volume: 41 start-page: e133 year: 2021 end-page: e144 ident: CR24 article-title: Moving beyond 3+3: the future of clinical trial design publication-title: Am. Soc. Clin. Oncol. Educ. Book doi: 10.1200/EDBK_319783 – ident: CR31 – volume: 35 start-page: 1317 year: 2014 end-page: 1326 ident: CR29 article-title: Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: a double-blind, randomized, placebo-controlled phase II study publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000000466 – volume: 9 start-page: 710159 year: 2021 ident: CR16 article-title: Hair cell generation in cochlear culture models mediated by novel γ-secretase inhibitors publication-title: Front. Cell Dev. Biol. doi: 10.3389/fcell.2021.710159 – volume: 27 start-page: 912 year: 2022 end-page: 922 ident: CR10 article-title: The global hearing therapeutic pipeline: 2021 publication-title: Drug Discov. Today doi: 10.1016/j.drudis.2021.11.009 – volume: 26 start-page: 1313 year: 2018 end-page: 1326 ident: CR15 article-title: Regeneration of cochlear hair cells and hearing recovery through Hes1 modulation with siRNA nanoparticles in adult guinea pigs publication-title: Mol. Ther. doi: 10.1016/j.ymthe.2018.03.004 – volume: 397 start-page: 107922 year: 2020 ident: CR19 article-title: Extended high frequency hearing and speech perception implications in adults and children publication-title: Hear Res. doi: 10.1016/j.heares.2020.107922 – volume: 52 start-page: 360 year: 2013 ident: 45784_CR6 publication-title: Int J. Audio. doi: 10.3109/14992027.2013.769066 – volume: 397 start-page: 107922 year: 2020 ident: 45784_CR19 publication-title: Hear Res. doi: 10.1016/j.heares.2020.107922 – volume: 141 start-page: 3203 year: 2017 ident: 45784_CR22 publication-title: J. Acoust. Soc. Am. doi: 10.1121/1.4982923 – volume: 15 start-page: 51 year: 1986 ident: 45784_CR26 publication-title: Scand. Audio. doi: 10.3109/01050398609045954 – volume: 14 start-page: 350 year: 2009 ident: 45784_CR25 publication-title: Audio. Neurootol. doi: 10.1159/000241892 – ident: 45784_CR30 – volume: 38 start-page: 792 year: 2017 ident: 45784_CR7 publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000001427 – volume: 41 start-page: e133 year: 2021 ident: 45784_CR24 publication-title: Am. Soc. Clin. Oncol. Educ. Book doi: 10.1200/EDBK_319783 – volume: 42 start-page: e849 year: 2021 ident: 45784_CR20 publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000003120 – volume: 59 start-page: 33 year: 2020 ident: 45784_CR28 publication-title: Int J. Audio. doi: 10.1080/14992027.2019.1638526 – volume: 40 start-page: 6357 year: 2020 ident: 45784_CR4 publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.0937-20.2020 – volume: 66 start-page: 325 year: 2014 ident: 45784_CR21 publication-title: Indian J. Otolaryngol. Head. Neck Surg. doi: 10.1007/s12070-014-0721-7 – volume: 35 start-page: 1317 year: 2014 ident: 45784_CR29 publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000000466 – ident: 45784_CR12 – volume: 377 start-page: 2465 year: 2017 ident: 45784_CR3 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1616601 – ident: 45784_CR31 doi: 10.1097/MAO.0000000000001135 – volume: 40 start-page: 559 year: 2019 ident: 45784_CR8 publication-title: Otol. Neurotol. doi: 10.1097/MAO.0000000000002194 – volume: 77 start-page: 58 year: 2013 ident: 45784_CR14 publication-title: Neuron doi: 10.1016/j.neuron.2012.10.032 – volume: 26 start-page: 1313 year: 2018 ident: 45784_CR15 publication-title: Mol. Ther. doi: 10.1016/j.ymthe.2018.03.004 – volume: 380 start-page: 175 year: 2019 ident: 45784_CR9 publication-title: Hear Res doi: 10.1016/j.heares.2019.07.003 – volume: 31 start-page: 8351 year: 2011 ident: 45784_CR13 publication-title: J. Neurosci. doi: 10.1523/JNEUROSCI.6366-10.2011 – volume: 59 start-page: 567 year: 2020 ident: 45784_CR5 publication-title: Int J. Audio. doi: 10.1080/14992027.2020.1773550 – volume: 390 start-page: 2503 year: 2017 ident: 45784_CR1 publication-title: Lancet doi: 10.1016/S0140-6736(17)31073-5 – volume: 61 start-page: 1 year: 2022 ident: 45784_CR11 publication-title: Prog. Med Chem. doi: 10.1016/bs.pmch.2022.05.001 – volume: 4 start-page: 33 year: 2022 ident: 45784_CR23 publication-title: ENT Audioloy N. – volume: 27 start-page: 912 year: 2022 ident: 45784_CR10 publication-title: Drug Discov. Today doi: 10.1016/j.drudis.2021.11.009 – volume: 9 start-page: 710159 year: 2021 ident: 45784_CR16 publication-title: Front. Cell Dev. Biol. doi: 10.3389/fcell.2021.710159 – ident: 45784_CR2 – volume: 41 start-page: 365 year: 1978 ident: 45784_CR17 publication-title: J. Neurophysiol. doi: 10.1152/jn.1978.41.2.365 – volume: 11 start-page: 157 year: 2017 ident: 45784_CR18 publication-title: Front. 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