Evidence map›Paper›PMID 41537484›Full record

ArticleOtology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology2026

Pharmacologic Inhibition of JAK1/2 Potentiates Aminoglycoside-Induced Ototoxicity.

Jonathan Fleegel, Iman Ezzat, Sarath Vijayakumar, Marisa Zallocchi, Jian Zuo

Abstract read
In one paragraph

Article in Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Jonathan FleegelCreighton University, School of Medicine, Omaha, Nebraska.ORCID 0000-0001-5410-2721
Iman EzzatCreighton University, School of Medicine, Omaha, Nebraska.
Sarath VijayakumarCreighton University, School of Medicine, Omaha, Nebraska.
Marisa ZallocchiCreighton University, School of Medicine, Omaha, Nebraska.
Jian ZuoTing Therapeutics LLC, San Diego, California.

Funding

Genetic control of cellular conversion in the mature cochleaR01DC015010 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2016 to 2020
$2.3M
Discovery of In Vivo Small Molecules for Hearing Protection Against Cisplatin and NoiseR01DC015444 · NIDCD · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI ZUO, JIAN · 2016 to 2018
$1.6M
Repurposing momelotinib for the prevention of aminoglycoside-induced ototoxicityF30DC019528 · NIDCD · CREIGHTON UNIVERSITY · PI FLEEGEL, JONATHAN PAUL · 2021 to 2023
$129k
Dr. Richard J. Bellucci Family Foundation Predoctoral Research AwardNIDCD NIH HHS F30 DC019528NIDCD NIH HHS R01 DC015010NIDCD NIH HHS R01 DC015444
6 · The paper itself

Abstract

hypothesisIn our study, we investigated the ototoxic interaction of Janus kinase (JAK) inhibition in combination with aminoglycosides.

backgroundThe therapeutic landscape of JAK inhibitors has undergone a significant transformation since 2018, characterized by a rapid increase in FDA approvals for this class of drugs. Initially approved for conditions like myelofibrosis and polycythemia vera, the indications have expanded to include several inflammatory conditions, such as psoriatic arthritis, ulcerative colitis, and rheumatoid arthritis, leading to a substantial increase in patients exposed to these therapies. The potential interactions of this drug class with ototoxins are unknown.

methodsC57Bl/6N mice corrected for Cadherin23 (Cdh23 tm2.1/kjn ) were treated with kanamycin (KM), (500 mg/kg, subcutaneously, twice daily for 14 d) either alone or with lipopolysaccharide (LPS) (1 mg/kg, intraperitoneally, 3 times during the treatment) to mimic inflammation from gram-negative infections. A separate group also received momelotinib (MMB), a dual JAK1/JAK2 inhibitor, at 50 mg/kg or 20 mg/kg by oral gavage twice daily for 14 days alongside KM and LPS. Hearing function was assessed through auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE), while cochlear damage and hair cell loss were evaluated using whole mount staining for phalloidin and myosin 7a.

resultsInhibition of JAK1 and JAK2 by MMB caused a substantial increase in the hearing loss and cochlear damage in animals exposed KM and LPS as measured by ABR, DPOAE, and outer hair cell (OHC) counts.

conclusionJAK1 and JAK2 inhibition worsens cochlear damage in mice exposed to aminoglycosides.

Indexed as

AminoglycosidesJanus Kinase 1Janus Kinase 2Janus Kinase InhibitorsKanamycinOtotoxicityAnimalsCochleaEvoked Potentials, Auditory, Brain StemLipopolysaccharidesMiceMice, Inbred C57BLAminoglycosidesJak1 protein, mouseJak2 protein, mouseJanus Kinase 1Janus Kinase 2Janus Kinase InhibitorsKanamycinLipopolysaccharidesAminoglycoside-induced ototoxicityJak inhibitorJanus kinaseKanamycinLipopolysaccharideMomelotinibOtotoxicityPreclinical animal models

Identifiers

PMID41537484
PMCPMC13082920

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.