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Protecting patients from hearing loss is critical for maintaining their quality of life. This study aimed to understand the onset of pathology in cochlear structure and function. By investigating patients and juvenile\n                    <jats:italic>Ndp<\/jats:italic>\n                    -mutant mice, we elucidated the sequence of onset of physiological changes (in auditory brainstem responses, distortion product otoacoustic emissions, endocochlear potential, blood-labyrinth barrier integrity) and determined the cellular, histological, and ultrastructural events leading to hearing loss. We found that cochlear vascular pathology occurs earlier than previously reported and precedes sensorineural hearing loss. The work defines a disease mechanism whereby early malformation of the cochlear microvasculature precedes loss of vessel integrity and decline of endocochlear potential, leading to hearing loss and hair cell death while sparing spiral ganglion cells. This provides essential information on events defining the optimal therapeutic window and indicates that early intervention is needed. In an era of advancing gene therapy and small-molecule technologies, this study establishes\n                    <jats:italic>Ndp<\/jats:italic>\n                    -mutant mice as a platform to test such interventions and has important implications for understanding the progression of hearing loss in Norrie disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.148586","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T14:00:56Z","timestamp":1644242456000},"source":"Crossref","is-referenced-by-count":15,"title":["The timing of auditory sensory deficits in Norrie disease has implications for therapeutic intervention"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-4796","authenticated-orcid":true,"given":"Dale","family":"Bryant","sequence":"first","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, University College London, and NIHR Great Ormond Street Hospital Biomedical 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