A novel combination of drug therapy to protect residual hearing post cochlear implant surgery

Eshraghi, Adrien A.; Roell, Jonathan; Shaikh, Noah; Telischi, Fred F.; Bauer, Blake; Guardiola, Mateo; Bas, Esperanza; Water, Thomas Van De; Rivera, Ileana; Mittal, Jeenu

doi:10.3109/00016489.2015.1134809

Cited by 18 publications

(15 citation statements)

References 20 publications

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“…However, by large, they revolve around ROS, inflammation and upregulation of pro-apoptotic pathways [8]. The hair cell death is the result of an increase in stress-induced, pro-apoptotic molecules such as TNF-α, IL-6, IL-1β, mitogen-activated kinase (MAPK), Bax, TNFR1, and Bax/Bcl-2 ratio and caspases [9,16]. These pro-apoptotic molecules can be the result of cellular stress from several sources including inflammation, Fas-receptor activation, DNA damage, or increased endoplasmic reticulum and mitochondrial membrane permeability [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…L-NAC is a free radical scavenger and a pro-drug for glutathione, the body's primary reductive enzyme, allowing it to effectively neutralize ROS and RNS [25]. In doing so, it protects against damage to DNA, proteins, and depletion of intracellular glutathione levels thereby reducing the activation of downstream pro-apoptotic molecules MAPK/JNK, NF-κB, caspase, and Src protein kinase [9,25,26]. Indeed, L-NAC has been shown to completely prevent hearing deficits and hair cell loss in glutathione deficient mice [26].…”

Section: Discussionmentioning

confidence: 99%

“…One challenge of CI surgery is the preservation of residual hearing [4,5]. CI can induce electrode insertion trauma (EIT) that can result in damage to critical sensory structures of the inner ear including the modiolus, spiral lamina, spiral ligament, stria vascularis, and the organ of Corti (OC) during initial electrode insertion [6][7][8][9][10]. Moreover, this immediate structural damage is followed by an inflammatory response mediated by the ischemia-reperfusion injury, immune cell recruitment and the generation of reactive oxygen species (ROS) which ultimately lead to further structural damage and apoptosis of hair cells [8].…”

Section: Introductionmentioning

confidence: 99%

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Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma

Eshraghi

Shahal

Davies

et al. 2020

JCM

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Background: Electrode insertion trauma (EIT) during cochlear implantation (CI) can cause loss of residual hearing. L-N-acetylcysteine (L-NAC) and dexamethasone (Dex) have been individually shown to provide otoprotection albeit at higher concentrations that may be associated with adverse effects. Objective/Aims: The aim of this study is to determine whether L-NAC and Dex could be combined to decrease their effective dosage. Materials and Methods: The organ of Corti (OC) explants were divided into various groups: 1) control; 2) EIT; 3) EIT treated with different concentrations of Dex; 4) EIT treated with different concentrations of L-NAC; 5) EIT treated with L-NAC and Dex in combination. Hair cell (HC) density, levels of oxidative stress, proinflammatory cytokines and nitric oxide (NO) was determined. Results: There was a significant loss of HCs in explants subjected to EIT compared to the control group. L-NAC and Dex in combination was able to provide significant otoprotection at lower concentrations compared to individual drugs. Conclusions and Significance: A combination containing L-NAC and Dex is effective in protecting sensory cells at lower protective doses than each compound separately. These compounds can be combined allowing a decrease of potential side effects of each compound and providing significant otoprotection for EIT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma

Eshraghi

Shahal

Davies

et al. 2020

JCM

Self Cite

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“…78–80 In cochlear implant explant rat and guinea pig cochlea, the administration of NAC partially preserved inner hair cells compared to controls in response to simulated surgical trauma. 81,82 …”

Section: Discussionmentioning

confidence: 99%

Emerging Therapies for Sensorineural Hearing Loss

Crowson

Hertzano

Tucci

2017

Otology &Amp; Neurotology

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Objective To critically review and evaluate the proposed mechanisms and documented results of the therapeutics currently in active clinical drug trials for the treatment of sensorineural hearing loss. Data Sources U.S. National Institutes of Health (NIH) Clinical Trials registry, MEDLINE/PubMed. Study Selection & Data Extraction A review of the NIH Clinical Trials registry identified candidate hearing loss therapies, and supporting publications were acquired from MEDLINE/PubMed. Proof-of-concept, therapeutic mechanisms, and clinical outcomes were critically appraised. Data Synthesis 22 active clinical drug trials registered in the United States were identified, and six potentially therapeutic molecules were reviewed. Of the six molecules reviewed, four comprised mechanisms pertaining to mitigating oxidative stress pathways that presumably lead to inner ear cell death. One remaining therapy sought to manipulate the cell death cascade, and the last remaining therapy was a novel cell replacement therapy approach to introduce a transcription factor that promotes hair cell regeneration. Conclusion A common theme in recent clinical trials registered in the United States appears to be the targeting of cell death pathways and influence of oxidant stressors on cochlear sensory neuroepithelium. In addition, a virus-delivered cell replacement therapy would be the first of its kind should it prove safe and efficacious. Significant challenges for bringing these bench-to-bedside therapies to market remain. It is never assured that results in non-human animal models translate to effective therapies in the setting of human biology. Moreover, as additional processes are described in association with hearing loss, such as an immune response and loss of synaptic contacts, additional pathways for targeting become available.

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“…Dexamethasone is already used to introduce the implant into the cochleostoma. It has been noticed that its use will result in a decrease in the chochlear lesions [8,25,27,45].…”

Section: Researches On Optimizing the Performance Of Current Implantsmentioning

confidence: 99%

Cochlear Implant Strategies and Biomaterials from Past to Future

Martu¹,

Cozma²,

Martu³

et al. 2017

Mat.Plast.

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The cochlear implant (C.I.) is a neurobionic prosthesis, being one of the greatest achievements of auditory neuroscience. Although C.I. represents the gold standard in the treatment of deafness in both the child and the adult, some problems like perception of speech in noise (atmosphere, environment), perception of music, binaural hearing remain, aspect to which improvements are expected. The article (this review) revises the road from the first attempts to cochlear implantation to today�s modern and reliable cochlear implant. Continuous improvement of existing technology both in terms of biomaterials used and in terms of speech processing and simultaneous stimulation strategies, promise with certainty the introduction of C.I. with superior performance. A look in the future is through new ideas and techniques, which await the transition from the experimental to the clinical stage in the emergence of a new generation of implants.

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A novel combination of drug therapy to protect residual hearing post cochlear implant surgery

Cited by 18 publications

References 20 publications

Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma

Evaluating the Efficacy of L-N-acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma

Emerging Therapies for Sensorineural Hearing Loss

Cochlear Implant Strategies and Biomaterials from Past to Future

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