Universal Recommendations on Planning and Performing the Auditory Brainstem Responses (ABR) with a Focus on Mice and Rats

Domarecka, Ewa; Szczepek, Agnieszka J.

doi:10.3390/audiolres13030039

Cited by 5 publications

(3 citation statements)

References 120 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, there are some differences that can affect species selection. Even if the hearing abilities of humans and laboratory animals overlap, hearing sensitivity is species dependent, especially in the high- and low-frequency ranges ( Heffner and Heffner, 2007 ; Lin et al, 2021 ; Domarecka and Szczepek, 2023 ). The optimal hearing frequency of mice, rats, and guinea pigs is higher than the optimal hearing frequency of humans.…”

Section: Ototoxicity Monitoring During Non-clinical Phasementioning

confidence: 99%

“…Therefore, the design and protocols for conducting this measure must be standardized to ensure reproducibility and accuracy of the results. A recent article gives recommendations on planning and performing the ABR with a focus on mice and rats ( Domarecka and Szczepek, 2023 ), to which scientists can refer to better understand how to measure ABR in rat and mice.…”

Section: Ototoxicity Monitoring During Non-clinical Phasementioning

confidence: 99%

See 1 more Smart Citation

Ototoxicity: a high risk to auditory function that needs to be monitored in drug development

Pasdelou,

Byelyayeva,

Malmström

et al. 2024

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Hearing loss constitutes a major global health concern impacting approximately 1.5 billion people worldwide. Its incidence is undergoing a substantial surge with some projecting that by 2050, a quarter of the global population will experience varying degrees of hearing deficiency. Environmental factors such as aging, exposure to loud noise, and the intake of ototoxic medications are implicated in the onset of acquired hearing loss. Ototoxicity resulting in inner ear damage is a leading cause of acquired hearing loss worldwide. This could be minimized or avoided by early testing of hearing functions in the preclinical phase of drug development. While the assessment of ototoxicity is well defined for drug candidates in the hearing field – required for drugs that are administered by the otic route and expected to reach the middle or inner ear during clinical use – ototoxicity testing is not required for all other therapeutic areas. Unfortunately, this has resulted in more than 200 ototoxic marketed medications. The aim of this publication is to raise awareness of drug-induced ototoxicity and to formulate some recommendations based on available guidelines and own experience. Ototoxicity testing programs should be adapted to the type of therapy, its indication (targeting the ear or part of other medications classes being potentially ototoxic), and the number of assets to test. For multiple molecules and/or multiple doses, screening options are available: in vitro (otic cell assays), ex vivo (cochlear explant), and in vivo (in zebrafish). In assessing the ototoxicity of a candidate drug, it is good practice to compare its ototoxicity to that of a well-known control drug of a similar class. Screening assays provide a streamlined and rapid method to know whether a drug is generally safe for inner ear structures. Mammalian animal models provide a more detailed characterization of drug ototoxicity, with a possibility to localize and quantify the damage using functional, behavioral, and morphological read-outs. Complementary histological measures are routinely conducted notably to quantify hair cells loss with cochleogram. Ototoxicity studies can be performed in rodents (mice, rats), guinea pigs and large species. However, in undertaking, or at the very least attempting, all preclinical investigations within the same species, is crucial. This encompasses starting with pharmacokinetics and pharmacology efficacy studies and extending through to toxicity studies. In life read-outs include Auditory Brainstem Response (ABR) and Distortion Product OtoAcoustic Emissions (DPOAE) measurements that assess the activity and integrity of sensory cells and the auditory nerve, reflecting sensorineural hearing loss. Accurate, reproducible, and high throughput ABR measures are fundamental to the quality and success of these preclinical trials. As in humans, in vivo otoscopic evaluations are routinely carried out to observe the tympanic membrane and auditory canal. This is often done to detect signs of inflammation. The cochlea is a tonotopic structure. Hair cell responsiveness is position and frequency dependent, with hair cells located close to the cochlea apex transducing low frequencies and those at the base transducing high frequencies. The cochleogram aims to quantify hair cells all along the cochlea and consequently determine hair cell loss related to specific frequencies. This measure is then correlated with the ABR & DPOAE results. Ototoxicity assessments evaluate the impact of drug candidates on the auditory and vestibular systems, de-risk hearing loss and balance disorders, define a safe dose, and optimize therapeutic benefits. These types of studies can be initiated during early development of a therapeutic solution, with ABR and otoscopic evaluations. Depending on the mechanism of action of the compound, studies can include DPOAE and cochleogram. Later in the development, a GLP (Good Laboratory Practice) ototoxicity study may be required based on otic related route of administration, target, or known potential otic toxicity.

show abstract

Section: Ototoxicity Monitoring During Non-clinical Phasementioning

confidence: 99%

Section: Ototoxicity Monitoring During Non-clinical Phasementioning

confidence: 99%

Ototoxicity: a high risk to auditory function that needs to be monitored in drug development

Pasdelou,

Byelyayeva,

Malmström

et al. 2024

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…One of the manuscripts in our special issue addresses this by providing recommendations for performing auditory brainstem response (ABR) in small animals. These recommendations developed by Domarecka et al are intended to improve the reproducibility of basic audiological research ("Universal Recommendations on Planning and Performing the Auditory Brainstem Responses (ABR) with a Focus on Mice and Rats") [2].…”

mentioning

confidence: 99%