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Progress Toward Drug Therapies for Hearing Loss

Research Findings

A report published in JAMA Otolaryngology‑Head and Neck Surgery just last week suggests that the number of people in the U.S. with hearing loss is expected to double by the year 2060.

Hearing loss comes in a few forms, but it is commonly acquired from excessive noise exposure, which can destroy the tiny, sound-sensing cells of the inner ear, known as “hair cells.” We are born with about 15,000 of these cells, and once we lose them (from noise, or perhaps from other factors such as certain medications, infection and as part of the natural aging process), we can’t get them back.

People meeting.
Albert Edge, Ph.D. (center), Director of the Tillotson Cell Biology Unit at Mass. Eye and Ear, meets with research fellows working in his lab aimed at restoring hearing through regenerating hair cells in the ear. Credit: John Earle.

Regenerating sound-sensing cells in the ear

Researchers around the world are working to find a solution (beyond hearing aids and cochlear implants) to overcome this debilitating condition. In 2013, a lab at Mass. Eye and Ear led by Albert Edge, Ph.D., successfully regenerated these tiny cells using stem cells (cells that divide and multiply) they had found in the inner ear. They found that they could convert the stem cells into hair cells using a combination of drugs and growth factors. They tested their method in a mouse model of acquired deafness, and restored partial hearing. However, the success of restoring hearing through this approach was limited by the small number of those stem cells found in the ear that could be turned into hair cells.

In a new research study published in Cell Reports, the lab collaborated with researchers at Brigham and Women’s Hospital and MIT to devise a 2-step plan for regenerating a large population of hair cells in the ear. The team has shown that they can first augment the number of stem cells, and then convert that large population into hair cells, lending hope that full hearing can be restored to those with hearing loss due to damaged hair cells.

The stem cells used to create hair cells, known as Lgr5+ cells, are also found in the lining of the intestine. In that environment, they contribute to the process of actively replacing the intestinal lining every eight days. The regenerative nature of these cells motivated the researchers to use investigate if they could be used to regenerate hair cells in the ear.

From cells extracted from a single ear, the team regenerated more than 11,500 cells in a dish (compared to 200 hair cells regenerated without efforts to augment).

When we discussed the advance with Dr. Edge, he said:

“This is an important step in our research that will hopefully bring treatments closer. We were excited to find Lgr5+ cells in the ear, because, in the intestine, these cells are very actively replacing the intestinal epithelium. Every eight days, we completely replace the entire lining of our intestine, making millions of new cells every day…Now, these cells appear very capable of making new hair cells in the ear. What we have done now in this work is to use a combination of drugs and growth factors to make these cells multiply. So, we can expand them to make thousands of cells, and then we can turn them into hair cells to be used for hearing.”

Though we still have a few more steps to take before we can design clinical trials (for humans) using this approach, the study certainly brings us closer to the goal of developing drug therapies for hearing loss.

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