Hair Loss

MIT researchers reverse hearing loss by regenerating inner ear hair growth

MIT researchers reverse hearing loss by regenerating inner ear hair growth

An MIT spin-off, Frequency Therapeutics, has a new drug candidate that stimulates the growth of hair cells in the inner ear.

Zach Winn | MIT News

Most of us know someone with hearing loss, but we may not fully understand the difficulties that lack of hearing can cause. Hearing loss can lead to isolation, frustration and a debilitating ringing in the ears known as tinnitus. It is also closely correlated with dementia.

Biotech company Frequency Therapeutics seeks to reverse hearing loss, not with hearing aids or implants, but with a new type of regenerative therapy that uses small molecules to program progenitor cells, a descendant of stem cells from the inner ear, to create the tiny hair cells that allow us to hear.

Hair cells die when exposed to loud noises or medications, including some 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, measured by speech perception tests, ie the ability to understand speech and recognize words.

“Speech perception is the #1 goal for improving hearing and the #1 need we hear from patients,” says Frequency Co-Founder and Chief Scientific Officer Chris Loose PhD.

In Frequency’s first clinical study, the company found statistically significant improvements in speech perception in some participants after a single injection, with some responses lasting nearly two years.

The company has dosed more than 200 patients to date and seen clinically significant improvements in speech perception in three separate clinical studies.


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Now Frequency is recruiting for a 124-person trial with preliminary results expected to be available early next year.

They believe they are making an important contribution to solving a problem that affects more than 40 million people in the United States and hundreds of millions more around the world.

“Hearing is such an important sense; it connects people to their community and cultivates a sense of identity,” says Harvard-MIT Health Sciences and Technology Affiliate Faculty Jeff Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential for hearing restoration will have a huge impact on society.”

From lab to patient

At MIT in 2005, Lucchino was an MBA student and Loose PhD candidate in chemical engineering when MIT Institute professor Robert Langer introduced the two aspiring entrepreneurs, and they began working on what would become Semprus BioSciences, a medical device company which they later sold for $80 million.

Eight years after playing matchmaker for Lucchino and Loose, Langer began working with Karp to study the lining of the human gut, which regenerates almost daily.

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Together with MIT postdoc Xiaolei Yin, who is now scientific advisor to Frequency, the researchers found that the same molecules that control stem cells in the gut are also used by a close descendant of stem cells called progenitor cells. Like stem cells, progenitor cells can develop into more specialized cells in the body.

Progenitor cells reside in the inner ear and generate hair cells when humans are in utero, but they become dormant before birth and never develop into more specialized cells such as the hair cells of the cochlea again. Humans are born with approximately 15,000 hair cells in each cochlea. These 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. Karp says no one had ever produced such large numbers of hair cells before. He still remembers looking at the results while visiting his family, including his father, who wears a hearing aid.

“I looked at them and said, ‘I think we have a breakthrough,'” Karp said. “This is the first and only time I’ve used that phrase.”

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The lead was enough for Langer to play matchmaker again and bring Loose and Lucchino into the fold to kick off Frequency Therapeutics.

The founders believe their approach – injecting small molecules into the inner ear to turn progenitor cells into more specialized ones – offers advantages over gene therapies, which can rely on extracting a patient’s cells, programming in the laboratory, then their delivery to the right region.

“Tissues in your body contain progenitor cells, so we see a huge range of applications,” Loose says. “We believe this is the future of regenerative medicine.”

Advancing Regenerative Medicine

The founders of Frequency were thrilled to see their lab work turn into an impactful drug candidate in clinical trials.

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“Some of these people [in the trials] couldn’t hear for 30 years, and for the first time they said they could walk into a crowded restaurant and hear what their kids were saying,” Langer says. “It’s so important to them. Obviously, there is still a lot to do, but just the fact that you can help a small group of people is really impressive to me.

Karp believes Frequency’s work will advance researchers’ ability to manipulate progenitor cells and lead to new treatments down the line.

“I wouldn’t be surprised if in 10 or 15 years, with the resources being put into this space and the incredible science that’s being done, we can get to the point where [reversing hearing loss] would be similar to Lasik surgery, where you go in and out in an hour or two and you can completely restore your vision,” says Karp. “I think we’ll see the same for hearing loss.”

“You always hope your work will have an impact, but it can take a long time for that to happen,” Karp says. “It has been an amazing experience working with the team to push this forward. There are already people in the trials whose hearing has improved dramatically and their lives have been changed. This impacts interactions with family and friends. It’s wonderful to be part of it.

(Reproduced with permission from MIT News; Edited for length)

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