Small Molecules to Provoke Regrowth of Hair Cells in the Inner Ear

There is some debate over whether age-related hearing loss is a matter of loss of hair cells in the inner ear, or a loss of the connections between those cells and the brain. Since various groups are working towards hair cell regeneration, including the one noted here, this debate should be resolved not too many years from now. The easiest way to answer questions of this nature, meaning which form of biological damage is the important one in a given age-related condition, is to fix that damage and see what happens.

The biotechnology company Frequency Therapeutics is seeking to reverse hearing loss - not with hearing aids or implants, but with a new kind of regenerative therapy. The company uses small molecules to program progenitor cells, a descendant of stem cells in the inner ear, to create the tiny hair cells that allow us to hear. Hair cells die off when exposed to loud noises or drugs including certain chemotherapies and antibiotics. Frequency's drug candidate is designed to be injected into the ear to regenerate these cells within the cochlea. In clinical trials, the company has already improved people's hearing as measured by tests of speech perception - the ability to understand speech and recognize words.

The company has dosed more than 200 patients to date and has seen clinically meaningful improvements in speech perception in three separate clinical studies. Another study failed to show improvements in hearing compared to the placebo group, but the company attributes that result to flaws in the design of the trial. Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.

Progenitor cells reside in the inner ear and generate hair cells when humans are in utero, but they become dormant before birth and never again turn into more specialized cells such as the hair cells of the cochlea. Humans are born with about 15,000 hair cells in each cochlea. Such cells die over time and never regenerate. In 2012, the research team was able to use small molecules to turn progenitor cells into thousands of hair cells in the lab. The researchers believe their approach offers advantages over gene therapies, which may rely on extracting a patient's cells, programming them in a lab, and then delivering them to the right area.

Link: https://news.mit.edu/2022/frequency-therapeutics-hearing-regeneration-0329

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