Figure 2.

Stages of degeneration in the cochlea may greatly affect the likelihood of success for cochlear gene therapies. Illustration of proposed four stages of disease progression in the cochlea caused by genetic mutations, as suggested by ocular gene therapy studies (Dalkara et al., 2016). Healthy cochlea is composed of health sensory cells (both IHCs and OHCs), supporting cells and cells in the SV. Deafness mutations may give rise to no significant cell death (A, defined as stage I), cell death primarily in (or started from) outer HCs (B, stage II), followed progressively and more severe degeneration stages of III (C, both inner and outer HCs are lost) and IV (D, all sensory and supporting cells are lost, leaving a layer of non-specific epithelial cells in the organ of Corti. SV is severely degenerated). According to results obtained from human clinical trials of ocular gene therapy, diseases at the stage III or stage IV have little chance for a successful outcome for gene therapy (Dalkara et al., 2016). In these cases, new strategies for applying gene therapy to restore hearing will need to be explored, and one is suggested in Figure 3.