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Menin-MLL inhibitors as a new therapeutic target for middle ear cholesteatoma
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Menin-MLL inhibitors as a new therapeutic target for middle ear cholesteatoma
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Journal Article
Menin-MLL inhibitors as a new therapeutic target for middle ear cholesteatoma
2026
Overview
Middle ear cholesteatoma (cholesteatoma), also known as a cholesteatomatous chronic otitis media, is concerning because it expands into the middle ear with bone destruction and causes irreversible hearing loss. Surgical resection is currently the only curative treatment, but the high recurrence rate remains a major problem, necessitating the development of novel therapies. In our previous study, we demonstrated that histone modifications are involved in the pathogenesis of cholesteatoma and that keratinocyte growth factor (KGF)-induced murine cholesteatoma is suppressed by administration of MI-503, a menin-MLL inhibitor. This study was designed to assess the therapeutic potential of menin-MLL inhibitors for the non-surgical management of cholesteatoma and to elucidate their mechanism of action. For the in vitro study, a growth inhibition assay was performed by administering menin-MLL inhibitors to mouse-derived primary tympanic membrane epithelial cells. For the in vivo study, menin-MLL inhibitors were topically administered into a KGF-induced murine cholesteatoma for seven consecutive days. The therapeutic effects on cholesteatoma were analyzed using micro-computed tomography imaging. The menin-MLL inhibitors reduced KGF-induced cholesteatoma in vivo (3/3, 100%). Among the menin-MLL inhibitors, BMF-219 (50 µM), a covalent menin inhibitor, showed the strongest inhibitory effect against cholesteatoma, with a 70.75 ± 8.92% rate of residual lesion. These findings show promising results for the therapeutic use of menin-MLL inhibitors in the non-surgical management of cholesteatoma.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 692/308
/ 692/699
/ Animals
/ Cholesteatoma, Middle Ear - drug therapy
/ Cholesteatoma, Middle Ear - metabolism
/ Cholesteatoma, Middle Ear - pathology
/ Eardrum
/ Epithelial Cells - drug effects
/ Epithelial Cells - metabolism
/ Histones
/ Humanities and Social Sciences
/ Humans
/ Leukemia
/ Mice
/ Myeloid-Lymphoid Leukemia Protein - antagonists & inhibitors
/ Myeloid-Lymphoid Leukemia Protein - metabolism
/ Proteins
/ Proto-Oncogene Proteins - antagonists & inhibitors
/ Proto-Oncogene Proteins - metabolism
/ Science
