Breakthrough Israeli study finds potential path to reversing hearing loss - The Jerusalem Post

A groundbreaking study by a team of researchers from Tel Aviv University’s Gray Faculty of Medical and Health Sciences offers hope to millions of people suffering from irreversible hearing loss.

The researchers identified a unique biological mechanism that could, in the future, enable the regeneration of sensory hair cells in the inner ear – a process previously thought to be impossible in humans.

The study was conducted under the leadership of Prof. Karen Avraham, who is dean of the faculty and holds the Dumont Chair for Research of Hearing Disorders.

It was spearheaded by Lama Khalaily, a TAU doctoral student, in collaboration with Prof. David Sprinzak of TAU’s Wise Faculty of Life Sciences; Shahar Kasirer from Sprinzak’s lab; Dr. Litao Tao of Creighton University in Omaha, Nebraska; and additional researchers.

The findings were published in the prestigious journal Science Advances under the title “Live imaging and multimodal profiling reveal transdifferentiation of a cochlear supporting cell subpopulation upon Notch inhibition.”

Hearing loss is often caused by damage to hair cells in the cochlea – cells responsible for detecting sound and converting it into electrical signals transmitted to the brain. Unlike many other species, mammals, including humans, are unable to regenerate these cells once they are damaged, which makes the loss permanent.

Cochlear implants – electronic devices inserted into the head that helps people with severe-to-profound sensorineural hearing loss perceive sound, bypass damaged hair cells in the inner ear, and stimulate the auditory nerve directly – are not ideal, Avraham told The Jerusalem Post in an interview. “They probably won’t be replaced completely by regenerated hair cells.”

The team uncovered a rare subset of supporting cells with an unexpected regenerative potential. Rather than responding uniformly, only a distinct group of cells entered a transitional state and began converting into hair cells, which exist naturally as a kind of “reserve population” that everyone has. Some people, however, may naturally have more regenerative potential than others, Avraham noted.

These cells, termed transdifferentiating Deiters’ cells (tDCs), are capable of making the transition from supporting cells to hair cells – a step that is vital for hair cell regeneration.

Using live tissue imaging and single-cell multi-omics methods that incorporate biological layers to trace the flow of information in a cell, “we focused on supporting cells that are adjacent to the hair cells. Under normal conditions, these cannot regenerate or transform into hair cells,” said Avraham.

To find out whether and how this limitation could be overcome, the TAU research team inhibited the Notch signaling pathway, a key communication mechanism between cells that is responsible for hair cell differentiation during embryonic development. The researchers found that these cells show unique genetic and epigenetic characteristics – changes in gene expression that act as chemical switches to turn genes on or off; are influenced by the environment, lifestyle, and development; and can be passed on during cell division. This enables them to respond to stimulation and initiate the regeneration process.

For the therapy, an injection could be made in the inner ear, but a surgeon would have to do it. Even five years ago, she said, “our discovery would not have been possible, because the technology used is new.”

Born in Canada, Avraham moved to the US at a young age. She received her bachelor’s degree in biology from Washington University in St. Louis and her doctorate from the Weizmann Institute of Science in Rehovot.

Her research focuses on the discovery and characterization of genes responsible for hereditary hearing loss. Using genetic, developmental, biochemical, cellular, and bioinformatic tools, her team studies the molecular basis of hearing loss.