January 11, 2017
Keio University School of Medicine
Japan Agency for Medical Research and Development (AMED)
A research team led by Professor Hideyuki Okano of the Department of Physiology and Professor Kaoru Ogawa of the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, in collaboration with Dr. Tatsuo Matsunaga, a director at NHO Tokyo Medical Center, has elucidated the cause of Pendred syndrome, a form of hereditary hearing loss, and discovered a new potential treatment using patient-derived iPS cells.
Pendred syndrome is a disease that causes progressive hearing loss, dizziness, and goiter. However, the development of treatments has been hampered because genetically modified mice do not develop progressive hearing loss as seen in humans.
The research team generated iPS cells from patients' blood, differentiated them into inner ear cells, and investigated the mechanism causing hearing loss. They found that abnormal PENDRIN protein accumulated exclusively within the inner ear cells from patients, forming aggregates similar to those seen in neurodegenerative diseases such as Alzheimer's disease. These inner ear cells were vulnerable to cellular stress, suggesting that the gradual progression of hearing loss is caused by inner ear cell death (the "inner ear degeneration" hypothesis).
Furthermore, the team searched for candidate drugs to prevent this cell death and, for the first time in the world, discovered that sirolimus (also known as rapamycin), a drug already used as an immunosuppressant, has potential therapeutic effects.
The inner ear is an organ located within bone and filled with lymph fluid, making it impossible to collect cells for examination or to observe the progression of hearing loss. This study, utilizing patient-derived iPS cells, has led to the unexpected finding that a phenomenon similar to that in Alzheimer's disease also occurs in the inner ear. This could bring about a major paradigm shift in hearing loss research, including for age-related hearing loss. Moreover, the method developed in this study for efficiently and stably generating inner ear cells from human iPS cells is expected to greatly contribute to the development of treatments for various hereditary hearing loss conditions that currently have no effective therapies, as well as to drug discovery research for hearing loss of unknown causes.
This research was published in "Cell Reports" on January 3, 2017.
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