Mar 15, 2019 Model provides new clues on genetic hearing loss

A laboratory testing model of Pendred syndrome, made from patient stem cells, gives new hope to those suffering from genetic hearing loss

A cochlear cell model made from patient blood cells revealed how the molecule pendrin (green)
malfunctions in those affected by Pendred syndrome

©  Reproduced from reference one under a Creative Commons Attribution (CC BY 4.0)

A new protocol for creating laboratory cell models, developed by a team of Japanese scientists, should expand potential options for treating genetically-based hearing loss.

Hearing loss does not just affect the elderly. More than 30 million children worldwide are estimated to suffer from hearing impairments, many of which have genetic causes. Roughly one in ten cases of hereditary hearing loss are diagnosed as Pendred syndrome, a condition which affects cells in the inner ear and thyroid, caused by mutations in a molecule called pendrin.

How mutations in pendrin lead to hearing loss — and how this could be best treated — has been unknown, in part because laboratory models of Pendred syndrome have not accurately reflected the disease, says Masato Fujioka, assistant professor from the Keio University School of Medicine. For one, when scientists mutated pendrin in mice, an animal model commonly used to study disease, the mice did not suffer progressive hearing loss over time, which is a characteristic symptom of Pendred syndrome.

“We knew the expression profile of deafness genes is sometimes different between species,” explains Fujioka. “So we thought that by developing human models using stem cells may give us new insights on the pathogenesis and models for drug screening.”

Fujioka and his colleagues have now published a new method for creating a cell model for Pendred syndrome, using cells derived from patients themselves.

To make their model, the researchers extracted white blood cells from the blood samples of three patients with Pendred syndrome. In the laboratory, the scientists first reprogrammed the blood cells to induced pluripotent stem cells (iPSCs) and then to a stable line of cochlear cells which they used for further analysis.

The team discovered from their new cell model that, in contrast to the existing beliefs, pendrin does not just malfunction in the cells of Pendred syndrome patients. Rather, it aggregates, causing cell stress and cell death.

Further, the team discovered using their model that they could reduce pendrin aggregation and cell death with low doses of the immunosuppressant rapamycin and the diabetes drug metformin. These drugs are already known to be protective against diseases other than hearing loss without severe side-effects. Following this finding, the study authors have begun a clinical trial testing rapamycin as a treatment for Pendred syndrome patients.

The scientists hope their protocol will lead to the development of therapeutics for a range of conditions. “We are now starting further iPSC-based drug development for another hereditary hearing loss condition,” says Fujioka.

The program-affiliated researchers contributing to this research are from the Keio University School of Medicine, Japan.


  1. Hosoya, M., Fujioka, M., Sone, T., Okamoto, S., Akamatsu, W. et al. Cochlear cell modeling using disease-specific iPSCs unveils a degenerative phenotype and suggests treatments for congenital progressive hearing loss. Cell Reports 18, 68-81 (2017). | Article

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