Early investigational drugs for hearing loss

Mukherjea, Debashree; Ghosh, Sumana; Bhatta, Puspanjali; Sheth, Sandeep; Tupal, Srinivasan; Borse, Vikrant; Brozoski, Thomas J.; Sheehan, Kelly; Rybak, Leonard P.; Ramkumar, Vickram

doi:10.1517/13543784.2015.960076

Cited by 27 publications

(23 citation statements)

References 105 publications

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“…With a better understanding of infectious disease-related hearing loss, however, novel therapies might emerge, such as the use of free radical scavengers 72 , anti-oxidants 73 and nanoparticle-based systems 74 . Surgical treatment might be beneficial in select cases in which there is an air-bone gap that is amenable to correction by surgical intervention.…”

Section: Managementmentioning

confidence: 99%

Congenital hearing loss

Korver

Smith

Camp

et al. 2017

Nat Rev Dis Primers

405

310

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Congenital hearing loss (hearing loss present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing-screening programmes enable early detection; early intervention will prevent delays in speech and language development and have long-lasting beneficial effects on social and emotional development and quality of life. A hearing loss diagnosis is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision-making and guide prevention and (genetic) counseling. Management options include specific antimicrobial therapies, surgical treatment of cranio-facial abnormalities and hearing aids. An improved understanding of the pathophysiology and molecular mechanisms underlying hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

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Section: Managementmentioning

confidence: 99%

Congenital hearing loss

Korver

Smith

Camp

et al. 2017

Nat Rev Dis Primers

405

310

View full text Add to dashboard Cite

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“…A principal cause of hearing loss is the death and/or dysfunction of the cells present in the organ of Corti 1 – 4 which cannot regenerate post-partum in mammals meaning loss of individual cell types is irreversible 5 . This condition, known as sensorineural hearing loss, is a global healthcare challenge with 600 million persons worldwide affected 6 . Presbycusis, the age-related decline in hearing capacity is possibly the most prevalent neurodegenerative disease of ageing 7 however chronic noise exposure and xenobiotic toxicity are significant contributing factors to hearing loss worldwide.…”

Section: Introductionmentioning

confidence: 99%

Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells

et al. 2018

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In view of the prevalence of sensorineural hearing defects in an ageing population, the development of protocols to generate cochlear hair cells and their associated sensory neurons as tools to further our understanding of inner ear development are highly desirable. We report herein a robust protocol for the generation of both vestibular and cochlear hair cells from human pluripotent stem cells which represents an advance over currently available methods that have been reported to generate vestibular hair cells only. Generating otic organoids from human pluripotent stem cells using a three-dimensional culture system, we show formation of both types of sensory hair cells bearing stereociliary bundles with active mechano-sensory ion channels. These cells share many morphological characteristics with their in vivo counterparts during embryonic development of the cochlear and vestibular organs and moreover demonstrate electrophysiological activity detected through single-cell patch clamping. Collectively these data represent an advance in our ability to generate cells of an otic lineage and will be useful for building models of the sensory regions of the cochlea and vestibule.

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“…While the intrinsic pathway activates with the release of cytochrome-c from the mitochondria, the extrinsic pathway activates by ligand binding to death receptors such as Fas and tumor necrosis factor receptor-1 (TNFR1) [3-7, 9, 10] . Some candidate agents such as sodium thiosulfate, D-or L-methionine, lipoic acid, N-acetyl cysteine, acetyl L-carnitine, alpha tocopherol, and resveratrol were studied both in vitro and in vivo to analyze their protective effects against CDDP-induced ototoxicity [7,16,[18][19][20][21] . However, none of them are currently approved for usage against CDDP-induced ototoxicity.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

Olgun¹,

Kırkım²,

Altun³

et al. 2016

Int Adv Otol

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1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained. In groups I, II, and III, only saline, KRG, and CDDP, respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP injections were administered on day 11. On day 14, final DPOAEs and ABR measurements were completed. The rats were then sacrificed, and their inner ear structures were evaluated by transmission electron microscopy. RESULTS:In the first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP ototoxicity. This protection was mainly due to a decline in apoptotic gene expression and an increase in antiapoptotic gene expression. In the in vivo part of the study, we found that both KRG doses had otoprotective effects. This protection was more prominent at the lower dose, especially on the spiral ganglion and the brainstem.CONCLUSION: KRG was shown to be an otoprotective agent against CDDP-induced ototoxicity both in vivo and in vitro.

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Early investigational drugs for hearing loss

Cited by 27 publications

References 105 publications

Congenital hearing loss

Congenital hearing loss

Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

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