Reversing hearing loss

Reprogramming enables regeneration of inner-ear cells.

One of the most common human sensory disorders, hearing loss, affects approximately one in 500 newborns and more than half of the population over 70 years of age. Notwithstanding its pervasiveness, there remain no accessible pharmacological treatments to treat hearing loss.

Now, scientists from the Harvard Medical School, along with Massachusetts Eye and Ear scientists, have taken a step forward towards developing treatments that regrow the missing cells that cause hearing loss.

They have developed a first of its kind of strategy to instigate cell division in the mature inner ear. Doing this, they can easily reprogram the inner ear’s cells to proliferate and regenerate hair cell-like cells in adult mice.

Senior study author Zheng-Yi Chen, HMS associate professor of otolaryngology-head and neck surgery and an associate scientist at the Eaton-Peabody Laboratories at Mass said, “This paper is the first to show that, by reprogramming, mature mammalian inner-ear cells can be induced to divide and become hair cells, which are needed for hearing. These findings of renewed proliferation and hair cell generation in a fully mature inner ear lay the foundation for the application of reprogramming and hair cell regeneration.”

In the past study, scientists have suggested that cells can be induced to divide and regenerate hair cells after damage in the newborn mouse inner ear. However, in fully mature ears, the capacity for cell division is lost, and hair cell regeneration does not occur. In humans, even a new inner ear is fully grown.

Thus, to develop new treatments for human hearing loss, it is essential to demonstrate that cell division and hair cell regeneration can be achieved in a mature mammalian inner ear.

Scientists, in this study, used a reprogramming approach by activating two molecular signals, Myc and Notch, in the adult ear. Doing this, they found that mature inner-ear cells can be induced to divide.

Importantly, some of the new cells developed characteristics of hair cells, including the presence of the transduction channels that complete the mechanical to electrical conversion and the capacity to shape associations with auditory neurons, the two of which are necessary to hear.

This work unveiled that reprogramming is achieved by reactivation of early inner-ear developmental genes so that the mature inner ear regains neonatal properties, which enables them to redivide and regenerate.

Chen said, “The most significant aspect of the current study is the fact that the fully mature mammalian inner ear still retains the capacity to divide and regenerate if it is sufficiently reprogrammed, which removes a fundamental barrier that has prevented the inner-ear regeneration necessary for hearing restoration.”

“We hope that our research can serve as a model for the regeneration of other tissues with similar properties that are unable to regrow cells, such as in the retina and the central nervous system.”

The study is published in the journal Nature Communications.

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