PMID- 37240591
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230530
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 12
IP  - 10
DP  - 2023 May 16
TI  - Potential Ototoxicity of Insulin-like Growth Factor 1 Receptor Signaling 
      Inhibitors: An In Silico Drug Repurposing Study of the Regenerating Cochlear 
      Neuron Transcriptome.
LID - 10.3390/jcm12103485 [doi]
LID - 3485
AB  - 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.
FAU - Bertagnoli, Lino E
AU  - Bertagnoli LE
AD  - Department of Otolaryngology-Head and Neck Surgery, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
AD  - Paracelsus Medical University, 5020 Salzburg, Austria.
FAU - Seist, Richard
AU  - Seist R
AD  - Department of Otolaryngology-Head and Neck Surgery, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
AD  - Paracelsus Medical University, 5020 Salzburg, Austria.
FAU - Batts, Shelley
AU  - Batts S
AD  - Department of Otolaryngology-Head and Neck Surgery, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
FAU - Stankovic, Konstantina M
AU  - Stankovic KM
AD  - Department of Otolaryngology-Head and Neck Surgery, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
AD  - Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 
      94305, USA.
AD  - Wu Tsai Neuroscience Institute, Stanford University, Stanford, CA 94305, USA.
LA  - eng
GR  - NIDCD grant U24-DC020857/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20230516
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC10218904
OTO - NOTNLM
OT  - adverse events
OT  - in silico drug repurposing
OT  - insulin-like growth factor 1 receptor inhibitor
OT  - ototoxicity
OT  - spiral ganglion neurons
OT  - teprotumumab
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/27 09:43
PMCR- 2023/05/16
CRDT- 2023/05/27 01:18
PHST- 2023/02/28 00:00 [received]
PHST- 2023/05/09 00:00 [revised]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2023/05/27 09:43 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:18 [entrez]
PHST- 2023/05/16 00:00 [pmc-release]
AID - jcm12103485 [pii]
AID - jcm-12-03485 [pii]
AID - 10.3390/jcm12103485 [doi]
PST - epublish
SO  - J Clin Med. 2023 May 16;12(10):3485. doi: 10.3390/jcm12103485.