Boosting auditory nerve function with cell therapy - status, surgical approach and potential candidates

Poor speech perception after cochlear implantation remains an important clinical problem, even when surgery is technically successful and rehabilitation is adequate. This heterogeneous "poor performer" phenotype can reflect device, electrode, cognitive, central-auditory, or neural factors, alone or in combination. A functionally competent auditory nerve is necessary for cochlear implant (CI) benefit, yet post-mortem studies have not shown a consistent relationship between absolute spiral ganglion neuron (SGN) counts and speech recognition. This suggests that neural function, rather than neuron number alone, is likely to be the limiting factor in many patients, and that otic neural progenitor (ONP) cell therapy is most plausible when loss of functional auditory neurons is itself the dominant, potentially treatable lesion. This review evaluates the evidence linking SGN integrity to CI outcomes, proposes a staged framework for identifying candidates for ONP therapy, appraises electrophysiological measures of neural function, and surveys surgical approaches for delivering cells to the human cochlea. Cadaveric and preclinical studies support the technical feasibility of surgical delivery, but current electrophysiological tools provide only indirect, largely within-patient information, and no single validated measure can yet identify SGN degeneration in an individual with the specificity required for trial inclusion. Ultimately, clinical benefit will depend on durable cell survival, correct differentiation and connectivity, and functional integration with CI stimulation. ONP therapy therefore represents a promising but still investigational strategy, whose path to the clinic will depend on rigorous patient stratification, validated diagnostic and outcome measures, and clear demonstration of long-term safety and efficacy.