Contemporary directions in the therapy of sensory hearing loss.

Abstract

<b>Introduction:</b> More than 5% of the world's population experience hearing impairment. The most common form is presbycusis (age-related hearing loss; ARHL). It affects almost one in three people over the age of 65. The hair cells of the cochlea play an important role in the process of sound registration. Genetic mutations, aging and environmental factors can cause damage that contributes to the hearing loss.<b>Methods and results:</b> The currently explored research directions include drug treatments, gene therapies, and stem cell therapies. To date, no significant differences in the therapeutic effect depending on the route of corticosteroid administration have been demonstrated in patients with moderate to severe hearing loss. New dexamethasone-containing hydrogel formulations, as well as lipid formulations, thermosensitive polymers, and nanoparticles, have been developed to achieve high drug concentrations in the inner ear structures. Otoprotective effects of antioxidants or substances that modify the toxic effects of e.g. cisplatin, are also being studied. Attempts at auditory cells' regeneration seem promising in hearing loss research. Substances that regulate the central mechanisms of the Notch and Wnt pathways are being explored to this end. The genetic determinants of presbycusis suggest that interference at the level of specific genes may be a promising option for the treatment of this condition. With the CRISPR/Cas9 technology, the functions of inner ear genes can be effectively studied by disrupting normal gene alleles. The CRISPR/Cas9 complexes developed to target specific genes are delivered using cationic lipids, proteins, and viral vectors. They are then transported through the round window membrane by diffusion, without the need to surgically disrupt the inner ear. The potential of using antisense oligonucleotides to treat hereditary deafness caused by hair cell degeneration has also been established. Another research direction is related to stem cells being used for the development of in vitro 3D models of the human inner ear. Studies are also pursued to identify the mechanisms underlying the formation of cochlear organoids from pluripotent cells as well as determine the critical time points and events for cochlear sensory epithelial development and targeted hair cell differentiation.<b>Conclusions:</b> In summary, significant progress has been made over the past decade in the search for novel therapies for sensory hearing loss. This line of research remains an ambitious and important area for further exploration.