Development and in vivo validation of small interfering RNAs targeting NOX3 to prevent sensorineural hearing loss

Nacher-Soler, German; Marteyn, Antoine; Barenzung, Natasha; Sgroi, Stéphanie; Krause, Karl‐Heinz; Senn, Pascal; Rousset, Francis

doi:10.3389/fneur.2022.993017

Cited by 5 publications

(4 citation statements)

References 40 publications

(31 reference statements)

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Section: Inner Ear and Gene Therapymentioning

confidence: 99%

“…Thanks to recent advances in understanding the genetic basis of several inner ear diseases, delivery of genetic material (DNA, RNA, siRNA, microRNA, antisense oligonucleotides, or CRISPR/Cas9) has emerged as a promising strategy for their treatment ( Lentz et al, 2020 ; Bankoti et al, 2021 ; Cui et al, 2022 ; Nacher-Soler et al, 2022 ). This approach aims to control gene replacement, silencing, augmentation, and editing and it could be an option to treat hearing loss and vestibular disorders ( Fukui and Raphael, 2013 ; Geng et al, 2018 ; Lentz et al, 2020 ; Bankoti et al, 2021 ; Cui et al, 2022 ; Nacher-Soler et al, 2022 ). The most common and successful way of delivering genetic material to the inner ear of rodents is through the RWM ( Akil et al, 2012 ; Askew et al, 2015 ; Pan et al, 2017a ; Emptoz et al, 2017 ; Landegger et al, 2017 ; Dulon et al, 2018 ) further highlighting the importance of perfecting this route of administration for future use in humans.…”

Section: Inner Ear and Gene Therapymentioning

confidence: 99%

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Precision medicine: a new era for inner ear diseases

Tavazzani,

Spaiardi,

Contini

et al. 2024

Front. Pharmacol.

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The inner ear is the organ responsible for hearing and balance. Inner ear dysfunction can be the result of infection, trauma, ototoxic drugs, genetic mutation or predisposition. Often, like for Ménière disease, the cause is unknown. Due to the complex access to the inner ear as a fluid-filled cavity within the temporal bone of the skull, effective diagnosis of inner ear pathologies and targeted drug delivery pose significant challenges. Samples of inner ear fluids can only be collected during surgery because the available procedures damage the tiny and fragile structures of the inner ear. Concerning drug administration, the final dose, kinetics, and targets cannot be controlled. Overcoming these limitations is crucial for successful inner ear precision medicine. Recently, notable advancements in microneedle technologies offer the potential for safe sampling of inner ear fluids and local treatment. Ultrasharp microneedles can reach the inner ear fluids with minimal damage to the organ, collect μl amounts of perilymph, and deliver therapeutic agents in loco. This review highlights the potential of ultrasharp microneedles, combined with nano vectors and gene therapy, to effectively treat inner ear diseases of different etiology on an individual basis. Though further research is necessary to translate these innovative approaches into clinical practice, these technologies may represent a true breakthrough in the clinical approach to inner ear diseases, ushering in a new era of personalized medicine.

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Section: Inner Ear and Gene Therapymentioning

confidence: 99%

Section: Inner Ear and Gene Therapymentioning

confidence: 99%

Precision medicine: a new era for inner ear diseases

Tavazzani,

Spaiardi,

Contini

et al. 2024

Front. Pharmacol.

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“…Similarly to the early loss of ribbon synapses (the highly specialized inner hair cells' tonic synapses) in age-, noise-, and aminoglycoside-induced hearing loss in animal models (Liu et al, 2013;Kujawa and Liberman, 2015;Xiong et al, 2020), cisplatin-induced synaptopathy may occur in humans as well. Indeed, the auditory synapse has been found to be the most vulnerable part of the cochlea regarding cisplatin ototoxicity in mice (Nacher-Soler et al, 2022).…”

Section: Limitations and Strengthsmentioning

confidence: 99%

“…Therefore, preventing ototoxic hearing loss through molecular or pharmacological intervention would interest thousands of patients worldwide. To this end, our and many other institutions currently undertake translational research projects aiming at otoprotection by different methods (Rousset et al, 2015;Waissbluth et al, 2017;Nacher-Soler et al, 2022). We believe that a strong collaboration between clinicians and basic scientists will significantly increase the chances of developing an effective preventive therapy against cisplatin ototoxicity in the future, tailored to the patient's need and with a meaningful mode of application for otologists.…”

Section: Otoprotectionmentioning

confidence: 99%

Incidence of cisplatin-induced ototoxicity in adult cancer patients based on audiometric confirmation of patient self-report

Voruz,

Vuilleumier,

Migliorini

et al. 2023

Front. Audiol. Otol.

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IntroductionRobust clinically relevant epidemiological and audiological data are needed to prepare for future clinical trials aiming at preventing cisplatin-induced ototoxicity in this suffering cancer population. We assessed the incidence, severity, and potential risk factors of symptomatic cisplatin-induced hearing loss in a large cohort of adults.MethodsRetrospective cohort study at a tertiary care university hospital. The study group included consecutive patients over 18 years old treated with cisplatin-based chemotherapy without concomitant inner ear radiotherapy or other ototoxic medication. Every participant underwent baseline pretreatment audiometry and was asked for audiological symptoms (tinnitus or subjective hearing loss) during the treatment. If symptomatic, comparative standard audiometry (0.125 to 8 kHz) was performed. Hearing loss was defined by a threshold shift ≥15 dB HL in at least one of the tested frequencies.ResultsA total of 401 cancer patients (59% males) with a mean age of 56 years (range 18-80) were included. Eighty-one patients (20%) developed symptomatic hearing loss, predominantly affecting the high frequencies from 4 to 8 kHz. Among them, 49 (60%) experienced simultaneous new-onset tinnitus. None of the analyzed potential risk factors (age, sex, smoking, hypertension, diabetes, dyslipidemia, chemotherapeutic regimen, and cumulative cisplatin dose) was statistically correlated with hearing loss.DiscussionAt least 1 out of 5 patients treated with cisplatin developed audiological symptoms associated with audiometric hearing loss within the 0.125 to 8 kHz range, for which new-onset tinnitus is a sensitive symptom. Not all audiological symptoms are accompanied by audiometric change. No predisposing factor could be identified. Standardized audiological monitoring before and during cisplatin-based chemotherapy allows quantitative assessment of early audiometric signs of ototoxicity, offering to optimize anticancer therapy while minimizing morbidity in a multidisciplinary setting.

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Nanodelivery of antioxidant Agents: A promising strategy for preventing sensorineural hearing loss

Hajmohammadi,

Bagher,

Taghizadeh-Hesary

et al. 2024

European Journal of Pharmaceutics and Biopharmaceutics

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Development and in vivo validation of small interfering RNAs targeting NOX3 to prevent sensorineural hearing loss

Abstract: Development and in vivo validation of small interfering RNAs targeting NOX to prevent sensorineural hearing loss.

Cited by 5 publications

References 40 publications

Precision medicine: a new era for inner ear diseases

Precision medicine: a new era for inner ear diseases

Incidence of cisplatin-induced ototoxicity in adult cancer patients based on audiometric confirmation of patient self-report

Nanodelivery of antioxidant Agents: A promising strategy for preventing sensorineural hearing loss

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