Potential Ototoxicity of Insulin-like Growth Factor 1 Receptor Signaling Inhibitors: An In Silico Drug Repurposing Study of the Regenerating Cochlear Neuron Transcriptome Article Swipe
Lino E. Bertagnoli
,
Richard Seist
,
Shelley Batts
,
Konstantina M. Stanković
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/jcm12103485
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/jcm12103485
Spiral ganglion neurons (SGNs) connect cochlear hair cells with higher auditory pathways and their degeneration due to drug toxicity (ototoxicity) contributes to hearing loss. This study aimed to identify drug classes that are negatively correlated with the transcriptome of regenerating SGNs. Human orthologs of differentially expressed genes within the regenerating neonatal mouse SGN transcriptome were entered into CMap and the LINCS unified environment and perturbation-driven gene expression was analyzed. The CMap connectivity scores ranged from 100 (positive correlation) to −100 (negative correlation). Insulin-like growth factor 1/receptor (IGF-1/R) inhibitors were highly negatively correlated with the regenerating SGN transcriptome (connectivity score: −98.87). A systematic literature review of clinical trials and observational studies reporting otologic adverse events (AEs) with IGF-1/R inhibitors identified 108 reports (6141 treated patients). Overall, 16.9% of the treated patients experienced any otologic AE; the rate was highest for teprotumumab (42.9%). In a meta-analysis of two randomized placebo-controlled trials of teprotumumab, there was a significantly higher risk of hearing-related (pooled Peto OR [95% CI]: 7.95 [1.57, 40.17]) and of any otologic AEs (3.56 [1.35, 9.43]) with teprotumumab vs. a placebo, whether or not dizziness/vertigo AEs were included. These results call for close audiological monitoring during IGF-1-targeted treatment, with prompt referral to an otolaryngologist should otologic AEs develop.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/jcm12103485
- https://www.mdpi.com/2077-0383/12/10/3485/pdf?version=1684225855
- OA Status
- gold
- Cited By
- 1
- References
- 66
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4377043340
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- OpenAlex ID
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https://openalex.org/W4377043340Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/jcm12103485Digital Object Identifier
- Title
-
Potential Ototoxicity of Insulin-like Growth Factor 1 Receptor Signaling Inhibitors: An In Silico Drug Repurposing Study of the Regenerating Cochlear Neuron TranscriptomeWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-05-16Full publication date if available
- Authors
-
Lino E. Bertagnoli, Richard Seist, Shelley Batts, Konstantina M. StankovićList of authors in order
- Landing page
-
https://doi.org/10.3390/jcm12103485Publisher landing page
- PDF URL
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https://www.mdpi.com/2077-0383/12/10/3485/pdf?version=1684225855Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2077-0383/12/10/3485/pdf?version=1684225855Direct OA link when available
- Concepts
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Medicine, Ototoxicity, Drug repositioning, Spiral ganglion, Transcriptome, Hearing loss, Adverse effect, Cochlear implant, Placebo, Pharmacology, Tinnitus, Internal medicine, Drug, Bioinformatics, Audiology, Gene, Pathology, Biology, Gene expression, Genetics, Chemotherapy, Alternative medicine, CisplatinTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2023: 1Per-year citation counts (last 5 years)
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66Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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