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Preclinical Models to Study the Molecular Pathophysiology of Meniere's Disease: A Pathway to Gene Therapy
Prathamesh T Nadar-Ponniah1, Jose A Lopez-Escamez1,2,3
1Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2065, Australia.
Abstract:
Background: Meniere's disease (MD) is a set of rare disorders that affects >4 million people worldwide. Individuals with MD suffer from episodes of vertigo associated with fluctuating sensorineural hearing loss and tinnitus. Hearing loss can involve one or both ears. Over 10% of the reported cases are observed in families, suggesting its significant genetic contribution. The condition is polygenic with >20 genes, and several patterns of inheritance have been reported, including autosomal dominant, autosomal recessive, and digenic inheritance across multiple MD families. Preclinical research using animal models has been an indispensable tool for studying the neurophysiology of the auditory and vestibular systems and to get a better understanding of the functional role of genes that are involved in the hearing and vestibular dysfunction. While mouse models are the most used preclinical model, this review analyzes alternative animal and non-animal models that can be used to study MD genes. Methods: A literature search of the 21 genes reported for familial MD and the preclinical models used to investigate their functional role was performed. Results: Comparing the homology of proteins encoded by these genes to other model organisms revealed Drosophila and zebrafish as cost-effective models to screen multiple genes and study the pathophysiology of MD. Conclusions: Murine models are preferred for a quantitative neurophysiological assessment of hearing and vestibular functions to develop drug or gene therapy.
Insights
This review explores alternative animal models for Meniere
Area of Science:
- Genetics and Genomics
- Neuroscience
- Otolaryngology
Background:
- Meniere's disease (MD) is a rare disorder affecting over 4 million people globally, characterized by vertigo, fluctuating hearing loss, and tinnitus.
- Familial cases suggest a significant genetic contribution, with over 20 implicated genes and various inheritance patterns (autosomal dominant, recessive, digenic).
- Preclinical models are crucial for understanding the neurophysiology of auditory and vestibular systems in MD.
Purpose of the Study:
- To review and analyze alternative animal and non-animal models for studying genes associated with Meniere's disease.
- To identify cost-effective models for screening MD genes and investigating disease pathophysiology.
- To compare the utility of different models for neurophysiological assessment and therapeutic development.
Main Methods:
- A comprehensive literature search was conducted on 21 genes reported in familial Meniere's disease.
- Preclinical models used to investigate the functional roles of these genes were identified and analyzed.
- Protein homology comparisons were made between human MD genes and model organisms.
Main Results:
- Drosophila and zebrafish emerged as cost-effective models for screening multiple Meniere's disease genes.
- These models are suitable for studying the pathophysiology of Meniere's disease.
- Murine models remain preferred for quantitative neurophysiological assessments of auditory and vestibular functions.
Conclusions:
- Alternative models like Drosophila and zebrafish offer valuable tools for early-stage Meniere's disease gene research.
- Murine models are essential for advanced neurophysiological studies and the development of targeted therapies.
- A multi-model approach is beneficial for comprehensive Meniere's disease research.
