Neomycin ototoxicity

Langman, Alan W.

doi:10.1177/019459989411000416

Cited by 2 publications

(1 citation statement)

References 31 publications

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“…According to the literature, an advantage of NAGs compared with AGs is the lack of oto- and nephrotoxicity [ 15 , 30 ], which makes NAGs potentially more appropriate for prolonged therapy requiring repetitive administration. While our finding that TC007 effectively stimulated PTC-readthrough makes this compound an interesting candidate, it has to be kept in mind that TC007 could exhibit ototoxic effects in vivo, similar to its AG precursor antibiotic neomycin [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia

Dąbrowski

Bukowy-Bieryłło

Jackson

et al. 2021

IJMS

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Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.

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Section: Discussionmentioning

confidence: 99%