Stem Cell and Genetic Therapies for Hair Cell-Related Hearing Loss

The exciting part of this-and it will be coming soon-is that we have candidate genes that stand out across all nine of these European populations studied, he said. Eventually, we expect to find additional genes of significance in presbycusis.

He noted that the discovery of disease-causing genes could potentially allow for diagnostics and biomolecules for the treatment of age-related hearing loss.

Sensory Hair Cell Function

Following Dr. Friedman, Dr. Segil described his studies, which could potentially lead to the genetic treatment of individuals who’ve lost sensory hair cell function. Noting that there are currently no therapies that can be claimed successful, he said research such as his provides hope for the future.

Unfortunately, mammalian hair cells do not regenerate and researchers don’t know why. It is possible that mammalian supporting cells may lack the capacity for regeneration of hair cells, or there may be a specialized type of supporting cell in vertebrates such as birds, which are capable of hair cell regeneration. Another possibility is that a signal for regeneration may be missing or blocked.

Dr. Segil noted that there are two possibilities for generating lost hair cells: (1) stimulating self-repair by targeting endogenous progenitors, i.e., supporting cells; or (2) the transplantation of exogenous stem cells or progenitors. His team studies supporting cell stimulation by focusing on the identification of cells that might be susceptible to manipulation.

In mice, Dr. Segil’s team tested the capacity of cochlear supporting cells to divide and transdifferentiate by using green fluorescent markers expressed only in supporting cells in the inner ear. With the resulting purified supporting cells, the scientists discovered that the cells were still capable of self-division. And, although these cells normally wouldn’t actively divide, under the culture conditions in the lab, they did.

If we keep these cells in culture for six days, some of the cells begin to differentiate as hair cells, he said, adding that they have not yet identified the stimulus for the division. What they did determine is that self-division is age-dependent, in early cells. It is important, Dr. Segil said, to further test whether self-division can be stimulated in mature cells.

In another study, Dr. Segil’s team is targeting one pathway that keeps cells next to each other from differentiating as the same cell type. They believe that supporting cells are being actively inhibited from becoming hair cells by this pathway. Additional projects look at cell differentiation to better understand the process by which the supporting cell differentiated state is maintained.