A research group at Jikei University School of Medicine has discovered that a drug currently being developed for acute leukemia, a "menin-MLL inhibitor," may be effective against a difficult-to-treat form of chronic middle ear disease called "cholesteatoma." Cholesteatoma involves a pearl-like white mass forming around the eardrum. Until now, surgery was the only option, but the disease is notorious for returning even after an operation. Medical treatment using medicine could pave the way for a much lighter burden on patients.
Lecturer Tomomi Fukuda, Lecturer Naotaro Akiyama, and Professor Hiromi Kojima (all in otology) of the Department of Otorhinolaryngology at the Jikei University School of Medicine, have been studying the mechanisms and treatments of middle ear cholesteatoma, which affects everyone from children to the elderly. Patients of this disease usually visit the doctor complaining of hearing loss or ear discharge. The disease is progressive, meaning the benign white mass grows while slowly dissolving the surrounding ear bones.
Surgery for this condition requires general anesthesia. Doctors use microscopes or endoscopes to shave away the ear bone and remove the mass. If the disease is advanced, the ossicles involved in hearing can be destroyed, requiring reconstructive surgery. Because the mass grows near the inner ear, facial nerves, and the brain, there are risks such as inner ear disorders (e.g. tinnitus, permanent hearing loss and dizziness), facial paralysis, meningitis, and brain abscess. Even after successful surgery, some reports show a 44% chance of the mass returning within ten years, making a non-surgical approach highly desirable to reduce the burden on patients.
The research group previously found that the disease is linked to "epigenetics," which is a system that controls how genes are turned on and off. The growth of the cells in a cholesteatoma is controlled by a group of proteins called the "menin-MLL complex." When this complex is active, it causes the cells to multiply. Therefore, in theory, if one can block the menin-MLL complex, the mass will stop growing.
In November 2025, in the field of hematology, the first menin inhibitor was approved in the United States for adult patients with relapsed or stubborn acute myeloid leukemia involving specific genetic mutations. This is a new type of "molecular targeted drug" that works by blocking the connection between the menin protein and another specific protein, effectively turning off the causative genes.
Fukuda and collaborators had previously developed a model mouse that successfully mimics the conditions of human middle ear cholesteatoma. They tested the menin-MLL inhibitor on these mice by applying it locally as ear drops to see if it would work. The results showed a reduction in size and a return to a healthy state after 7 days of administration. The team now aims to apply this discovery to human patients.
Fukuda commented: "Identifying the menin-MLL inhibitor, which was originally developed for leukemia, as a potential treatment for middle ear cholesteatoma is a major step forward. There are still hurdles to overcome before it can be delivered to patients as a therapeutic drug. Since this disease significantly lowers a patient's quality of life, we want to continue our research to offer an alternative to surgery."
The research was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. The results were published in the British online scientific journal Scientific Reports on January 26 and announced by Jikei University School of Medicine on January 27.
Original article was provided by the Science Portal and has been translated by Science Japan.