Non-GLP & GLP ototoxicity studies
Clinical data confirms that many therapeutic compounds, including those targeting indications unrelated to hearing and otic disorders, should be tested for auditory safety. Ototoxicity and associated auditory pathologies may affect millions of patients taking medication, potentially contributing to a diminished quality of life.
Currently, multiple drugs are being tested for repurposing to treat Covid-19. Some of them are listed among ototoxic agents, as they are known to induce side effects such as hearing loss, hyperacusis, tinnitus, or vertigo. Early assessment of auditory safety is essential to evaluate the risk-benefit balance of these drugs and define a minimum effective dose.
Additionally, several promising therapeutics and devices are currently in development for improving the lives of more than 500 million people suffering from hearing loss or tinnitus. The auditory safety of these solutions has to be tested before being approved by regulatory authorities.
CILcare provides unparalleled ototoxicity services that support early stage development and late-stage safety assessments.
NON-GLP ototoxicity studies
CILcare proposes different ototoxicity models to screen for potentially ototoxic compounds:
– In vitro culture of the organ of Corti with otic cell line: a valuable and rapid assay to screen a large number of therapeutic compounds. Learn more about CILcare’s in vitro screening model here.
– Ex vivo studies on cochlear explants: an excellent model to study the effect of a drug candidate on various cochlear cell types. Cochlear explant studies allow to count hair cells, supporting cells, fibroblasts, hair bundles, Planar Cell Polarity, synapses, and nerves.
– Zebrafish lateral line: a relevant, accurate, and fast starting in vivo model to identify potentially ototoxic drugs. Neuromast hair cells in zebrafish are similar in structure and function to the inner ear hair cells in mammals. They are easily visualized and counted.
CILcare offers preclinical studies to assess potential ototoxicity of therapeutics in rodents and larger animals using functional, behavioural, and morphological read-outs. Whether you are looking to evaluate the own effects of your drug candidates or to compare them with an ototoxic reference
compound, CILcare is able to provide you with exactly what you need to develop therapies that are safe for the inner ear.
Study evaluation includes:
– ABR & DPOAE to assess the activity and integrity of inner hair cells and the auditory nerve (ABR) and outer hair cells (DPOAE)
– Wave I analysis to study synaptic function
– GPIAS to assess the presence of tinnitus
– Histopathology with hair cells & ribbon synapses count to evaluate cochlear damage
Histopathology of middle and innner ear, H&E staining
Services provided in partnership with CBSET
The auditory specialists at CILcare and the Boston-based GLP-compliant CRO CBSET, Inc. have created a strategic alliance to offer drug and device developers cutting-edge preclinical services for the evaluation of auditory functions in a regulated GLP environment.
How to evaluate auditory safety ?
FDA guidance documents specify auditory safety evaluation utilizing two methodologies* :
1/ In vivo assessment : measure of Auditory Brainstem Responses (ABR)
Auditory Brainstem Responses (ABR)are electric potentials recorded from scalp electrodes. This non-invasive method allows to determine auditory response threshold. It is translational between rodents and human, and is commonly used for screening newborns.
2/ Ex vivo assessment : cytocochleogram
The cytocochleogram allows histopathological assessment of ototoxic damage on inner hair cells and outer hair cells of the cochlea, with anatomical localization corresponding to predicable patterns of functional deficits.
Fortify your IND application
CILcare and CBSET combine scientific excellence in otology with experienced, GLP-compliant, preclinical experience to reduce risk in your regulatory filings. From general toxicology studies to surgical services, our team has the capability to customize a full preclinical program in line with your IND approach and project milestones. The collaboration between CILcare and CBSET creates a highly experienced team offering complex transtympanic and intracochlear drug delivery methods which limit systemic exposure and provide robust, reproducible data in support of your ototoxicity or auditory function program.