The stem cell therapy that could reverse hearing loss

Frequency Therapeutics is betting that it can change the lives of millions of Americans with hearing loss, by triggering the body’s natural ability to heal itself.

Researchers have used cells in regenerative medicine for decades – in 1931, the father of cell therapy, Paul Niehans, treated a patient with material from calf embryos. Although today’s healthcare practitioners have left bovine embryonic cells behind, procedures such as bone marrow transplants are routinely used to replenish a patient’s cells after they’ve been destroyed.

When scientists first derived stem cells in 1981 – a decade after Niehans’s death – many heralded the innovation as a new chapter in regenerative medicine. Stem cells, with their ability to proliferate and differentiate into a variety of cell types, opened up entirely new avenues of research.

Today, many companies use scaffolds seeded with stem cells to trigger the body’s natural healing abilities. But MIT professor Robert Langer and Harvard professor Jeff Karp, the co-founders of Frequency Therapeutics (Woburn, Mass.), had a different idea: They see enormous potential in another type of differentiated cell called progenitor cells.

“We think we’re leading the revolution for ‘Regenerative Medicine 2.0,’” said Frequency Therapeutics co-founder and COO Chris Loose. “As we look back, we think maybe this is the way that regenerative medicine should have been done in the first place.”

Another, special type of cell

Every human being is born with tens of thousands of hair cells in the ear’s cochlea that move in response to sound. But noise exposure, age and other factors combine over time to cause the hairs to die off. And although animals including birds and reptiles can regrow the aural hair cells in their ears, mammals cannot – even though we have the “fundamental machinery” to regrow them, said Frequency co-founder and CEO David Lucchino.

For Frequency Therapeutics, the key discovery was that the mechanism, triggered via progenitor cells, is already present in the inner ear, Lucchino explained. Progenitor cells are similar to stem cells in that they can form into many different types of cells, although not as many types and not indefinitely. Think of progenitor cells as more mature versions of a typical stem cell, that only divide spontaneously during certain stages of human development.

Langer and Karp discovered that the epithelium in the human GI tract is filled with hyper-active progenitor cells that drive the epithelium in the GI tract to regenerate itself every five days. These particular progenitor cells, united by a similar activation pathway, are also found in the inner ear, eye, skin and pancreas, but they are especially active in the GI tract.

Once they figured out how those cells were activated, the researchers had an idea: What if you could activate the progenitor cells that live in a human’s ear and trigger them to regrow the inner ear hairs to recover hearing?

“When people began ‘Progenitor Medicine 1.0,’ they would take cells out of the body, manipulate them and try to put them back in the right place and get them to integrate and do the right job. That’s really complicated, particularly from a cell delivery and integration perspective,” Loose explained.

Instead, Frequency Therapeutics developed a proprietary combination of small molecule drugs that’s injected into the ear to activate the progenitor cells. The company plans to use a clinically-established injection into the middle ear of a slow-release gel, in a 3-minute office procedure that’s been used for years to administer drugs to treat ear infections.

Disruption demands bold leadership and powerful technology

The team at Frequency Therapeutics, which has 12 full-time employees, believe that their progenitor cell activation technique will be disruptive in regenerative medicine. Lucchino, who led Semprus Biosciences to an $80 million acquisition by Teleflex in 2012, said that truly disruptive companies need to unite strong technology and intellectual property – which is easier said than done.

“If it was easy, everyone would do it, and then it wouldn’t be disruptive,” Lucchino said. “Partly what allows us to be a so-called ‘disruptor’ is that Langer and Karp did all the early intellectual property work.”

Betting on technology to fundamentally change a field is risky; Loose pointed out that disruptive companies need to seek out leadership that’s willing to think big.

“I think you need founders and a board to think boldly and be comfortable trying to create very new types of therapies that may take some time, but can finally create a great deal of value,” he noted. “I think it’s easy, in a startup company when there’s so much risk, to try and focus on just building onto something that’s been done and making it a little bit better. There’s kind of a safety involved in that.”

But when MIT’s Langer – who has launched dozens of companies and is said to be the world’s most-cited engineer – is involved with a startup, he isn’t usually looking to make a small change in a scientific field.

“Disruptive is the opposite of incremental,” he told us. “Incremental change certainly happens, but fundamental changes – they’re much rarer. I think that’s what Frequency could be.”

It’s all about the patient

Nearly 40 million Americans suffer from some degree of hearing loss for which there is no therapy. Lucchino often receives emails from people looking to be a part of clinical trials, he said, crediting them as the driving force behind Frequency’s work.

“The goal is impact,” he said. “How can you help the most people? And by doing right by the patient, it’s going to lead you to a highly innovative place.”

Loose said working with Frequency Therapeutics and its progenitor cell activation technology reminds him of Langer’s advice when Loose was a graduate student at the Massachusetts Institute of Technology: “It takes the same amount of work to solve a really important problem as it does an unimportant problem, so work on something that’s really important.” “