Future Pharmacotherapy for Sensorineural Hearing Loss by Protection and Regeneration of Auditory Hair Cells

Matsunaga, Mami; Nakagawa, Takayuki

doi:10.3390/pharmaceutics15030777

Cited by 8 publications

(5 citation statements)

References 98 publications

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“…Numerous signaling pathways and factors, such as Notch, Wnt, and Atoh1, emerge as promising candidates to further investigate in hair cell regeneration studies within clinical trials. Several ongoing clinical studies are exploring the efficacy and safety of these pathways as potential therapeutic targets for hearing loss and in translational research in this field (ISRCTNregistry, 2017;ClinicalTrials.gov, 2022a,b;EU Clinical Trials Register, 2022;Matsunaga and Nakagawa, 2023).…”

Section: Figurementioning

confidence: 99%

Insights into the regulation of hearing regeneration

Khalaily,

Avraham

2024

Front. Audiol. Otol.

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Our perception of sound is mediated by sound-sensitive hair cells in the inner ear, located in a specialized neuro-epithelium that transmits information to the auditory cortex via the auditory pathway. A major cause of hearing loss is damage to and the death of these sensory hair cells. In humans, hair cells are only generated during embryonic development and cannot be replaced if damaged due to aging, excessive noise, ototoxic drugs, or illness. Much research is currently being invested worldwide in identifying methods to improve the ability to regenerate hair cells and circumvent their age-dependent limitations. Compared to numerous studies focused on gene therapy to restore deafness caused by a specific mutation before the onset of hair cell damage, research on auditory epigenetics is relatively recent. Although research indicates that epigenetic alterations play a crucial role in the differentiation, development, and regeneration of auditory hair cells, a dearth of comprehensive knowledge still exists regarding the specific role played by epigenetic modifications in the auditory system, with a particular emphasis on their potential correlation with the function and development of the auditory system. In addition, these modifications have been linked to the regeneration of hair cells caused by using pharmaceutical inhibitors (e.g., inhibition of the Notch pathway) and genetic (e.g., induced Atoh1 expression) treatments, which can lead to regenerating hair cells and restoring hearing. Recent developments in targetable epigenome-editing tools, such as CRISPR, and direct reprogramming enable targeted genome editing. In addition, the emergence of organoids and epigenetic drugs presents novel prospects for hearing restoration by manipulating regeneration pathways, making them promising methods for future regenerative treatments for hair cells. The potential of epigenetic modifiers as viable targets for pharmacological manipulation is becoming evident. Future therapies aimed at hair cell regeneration are particularly beneficial because of their advantage of restricting drug exposure within the inner ear.

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Section: Figurementioning

confidence: 99%

Insights into the regulation of hearing regeneration

Khalaily,

Avraham

2024

Front. Audiol. Otol.

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“…Although research on human inner ear regeneration has just started, some researchers have initiated clinical trials targeting either cochlear endogenous progenitor cells or ribbon synapses as a treatment for SNHL in adults (for an extended review on this topic, see [192,193]). The REGAIN clinical trial (EudraCT number 2016-004544-10) reported positive results from a phase I multiple ascending dose, open-label safety study of a novel gamma-secretase (Notch) inhibitor (LY3056480) in 15 patients with mild to moderate SNHL.…”

Section: Human Inner Ear Regeneration and Clinical Trials Targeting E...mentioning

confidence: 99%

“…Furthermore, a pioneer clinical trial has already shown that modulating Wnt (CHIR99021) and Notch (LY411575) signaling pathways with a recently commercialized drug (FX322) in patients with SNHL improves speech recognition in-quiet and in-noise 90 days after treatment [194]. Several clinical trials are ongoing to test the efficacy of FX322 to improve hearing in stable, acquired, adult-onset SNHL associated with noise-induced, idiopathic sudden, and age-related SNHL [192]. No results have yet been published on these ongoing clinical trials.…”

Section: Human Inner Ear Regeneration and Clinical Trials Targeting E...mentioning

confidence: 99%

Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions

Smith-Cortinez

Tan

Stokroos

et al. 2023

IJMS

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Sensorineural hearing loss is caused by damage to sensory hair cells and/or spiral ganglion neurons. In non-mammalian species, hair cell regeneration after damage is observed, even in adulthood. Although the neonatal mammalian cochlea carries regenerative potential, the adult cochlea cannot regenerate lost hair cells. The survival of supporting cells with regenerative potential after cochlear trauma in adults is promising for promoting hair cell regeneration through therapeutic approaches. Targeting these cells by manipulating key signaling pathways that control mammalian cochlear development and non-mammalian hair cell regeneration could lead to regeneration of hair cells in the mammalian cochlea. This review discusses the pathways involved in the development of the cochlea and the impact that trauma has on the regenerative capacity of the endogenous progenitor cells. Furthermore, it discusses the effects of manipulating key signaling pathways targeting supporting cells with progenitor potential to promote hair cell regeneration and translates these findings to the human situation. To improve hearing recovery after hearing loss in adults, we propose a combined approach targeting (1) the endogenous progenitor cells by manipulating signaling pathways (Wnt, Notch, Shh, FGF and BMP/TGFβ signaling pathways), (2) by manipulating epigenetic control, and (3) by applying neurotrophic treatments to promote reinnervation.

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“…Sensorineural hearing loss (SNHL) is a common otolaryngologic disorder characterized by damage to the auditory nerve resulting in decreased or complete loss of hearing ( Gregory et al, 2023 ; Matsunaga and Nakagawa, 2023 ; Zine and Fritzsch, 2023 ). The incidence of this disease has been increasing in recent years, which may be associated with factors such as fast-paced lifestyles, high-intensity work, and environmental noise pollution in modern society ( Al-Azzawi and Stapleton, 2023 ; Saba et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Research progress on the treatment and nursing of sensorineural hearing loss

et al. 2023

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This article provides a comprehensive review of the progress in the treatment and care of sensorineural hearing loss (SNHL), which is a common disease in the field of otolaryngology. In recent years, the incidence of SNHL has been on the rise due to factors such as fast-paced lifestyles, work pressure, and environmental noise pollution, which have a significant impact on the quality of life of patients. Therefore, the study of the treatment and care of SNHL remains a hot topic in the medical community. Despite significant advances in this field, there are still some challenges and limitations. For example, there is currently no single method that can completely cure SNHL, and the effectiveness of treatment may vary significantly among individuals. In addition, due to the complex etiology of SNHL, the prognosis of patients may vary greatly, requiring the development of personalized treatment plans and care strategies. To address these challenges, continuous research is needed to explore new treatment methods and care models to improve the quality of life of patients. In addition, there is a need for health education programs for the general public to raise awareness of SNHL and promote preventive measures to reduce its incidence. The ultimate goal is to ensure the sustainable development of the field of SNHL treatment and care, thus ensuring the health and well-being of affected individuals.

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Future Pharmacotherapy for Sensorineural Hearing Loss by Protection and Regeneration of Auditory Hair Cells

Cited by 8 publications

References 98 publications

Insights into the regulation of hearing regeneration

Insights into the regulation of hearing regeneration

Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions

Research progress on the treatment and nursing of sensorineural hearing loss

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