MIT scientists develop new regenerative drug that reverses hearing loss

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These images show cell regeneration, in pink, in a preclinical model of sensorineural hearing loss. The control is on the left and the right has been processed. Credit: Hinton AS, Yang-Hood A, Schrader AD, Loose C, Ohlemiller KK, McLean WJ.

When exposed to loud sounds or medicines, such as certain chemotherapies and antibiotics, hair cells die. The medication candidate developed by Frequency is intended to be injected into the ear to rebuild these cells inside the cochlea. The organization has already enhanced people’s hearing in clinical trials, as judged by speech perception tests – the capacity to interpret and distinguish words.

“Speech perception is the No. 1 goal for improving hearing and the No. 1 need we hear from patients,” Frequency co-founder and Chief Scientific Officer Chris Loose PhD ’07 states.

After a single injection, several subjects showed statistically significant improvements in speech perception, with some responses lasting almost two years in Frequency’s first clinical research.

To date, the company has dosed over 200 people and found clinically significant improvements in speech perception in three different clinical investigations. Another study found no difference in hearing between the treatment group and the placebo group, however, the manufacturer attributes this to problems in the trial’s design.

Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.

FREQ 162, Progenitor Cells

These two images show that one of Frequency’s lead compounds, FREQ-162, drives progenitor cells to turn into oligodendrocytes. The control is on the left and the right has been treated. Credit: Frequency Therapeutics

The company’s founders, including Loose, MIT Institute Professor Robert Langer, CEO David Lucchino MBA ’06, Senior Vice President Will McLean PhD ’14, and Harvard-MIT Health Sciences and Technology affiliate faculty member Jeff Karp, are already gratified to have been able to help people improve their hearing through the trials. They also believe they’re making important contributions toward solving a problem that impacts more than 40 million people in the U.S. 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 Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential to restore hearing will have enormous impact on society.”

From the lab to patients

In 2005, Lucchino was an MBA student in the MIT Sloan School of Management and Loose was a PhD candidate in chemical engineering at MIT. Langer introduced the two aspiring entrepreneurs, and they started working on what would become Semprus BioSciences, a medical device company that won the MIT $100K Entrepreneurship Competition and later sold at a deal valued at up to $80 million.

Frequency Therapeutics Founders

Frequency Therapeutics co-founders Will McLean, PhD recipient at the Harvard-MIT Division of Health Sciences and Technology (HST), David Lucchino MBA ’06, Jeff Karp, PhD, HST affiliate faculty and Professor at Brigham and Women’s Hospital, and Chris Loose, PhD ’07. Frequency went public on the Nasdaq on October 3, 2019. Credit: Courtesy of Frequency Therapeutics

“MIT has such a wonderful environment of people interested in new ventures that come from different backgrounds, so we’re able to assemble teams of people with diverse skills quickly,” Loose says.

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

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

“Every time we make an advance, we take a step back and ask how this could be even bigger,” Karp says. “It’s easy to be incremental, but how do we take what we learned and make a massive difference?”

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. Karp says no one had ever produced such a large number 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 says. “That’s the first and only time I’ve used that phrase.”

The advance was enough for Langer to play matchmaker again and bring Loose and Lucchino into the fold to start Frequency Therapeutics.

The founders believe their approach — injecting small molecules into the inner ear to turn progenitor cells into more specialized cells — 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.

“Tissues throughout 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

Frequency’s founders have been thrilled to watch their lab work mature into an impactful drug candidate in clinical trials.

“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.”

The company is also developing a drug for multiple sclerosis (MS), a disease in which the immune system attacks the myelin in the brain and central nervous system. Progenitor cells are already transforming into myelin-producing cells in the brain, but not fast enough to match the losses suffered by MS patients. Most MS treatments focus on suppressing the immune system rather than generating myelin.

Early versions of this drug candidate showed dramatic increases in myelin in mouse studies. The company plans to file an Investigational New Drug Application for MS with the FDA next year.

“When we designed this project, we wanted it to be a platform that could be widely applicable to multiple fabrics. Now we move into remyelination work, and to me that’s the tip of the iceberg in terms of what can be done by taking small molecules and controlling the local biology,” Karp says.

For now, Karp is already thrilled with Frequency’s progress, which struck him the last time he was in Frequency’s office and met a speaker who shared her experience with hearing loss.

“You always hope your work will have an impact, but it can take a long time for that to happen,” says Karp. “It’s 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.

If you would like to participate in the trial, you can find more information here.

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