Fully functioning hair cells (stained blue) produced by the researchers are capable of receiving signals through their hair-like stereocilia (stained pink) and transmitting signals to the brain.

The Division of Engineering in Medicine brings together a talented group of biomedical engineers. Immersed in the hospital environment, these bioengineers come from diverse scientific backgrounds and work across multiple disciplines, including materials science, nanotechnology, immunology, and biological sciences. This is the second in a series of stories about how these investigators translate understandings of biology into novel diagnostic materials, medical devices and therapies.

What if there was a drug that could restore hearing? Chronic hearing loss affects hundreds of millions of people across the world, and yet no treatment exists. Once a person loses a hair cell — a cell responsible for hearing — it never grows back, and the stem cells that generate new hair cells remain dormant throughout our lives. But what if we could bring these dormant cells “back to life” with a drug?

“To examine this question, we needed to better understand tissue regeneration, so we looked at the most active area of regeneration in the human body: the lining of the digestive tract, where cells regenerate more frequently than any other place,” saidJeff Karp, PhD, a bioengineer and professor in the Division of Engineering in Medicine.

To determine what encourages these cells to regenerate with such high frequency, Karp examined dozens of molecular signaling pathways in the intestinal lining. In collaboration with Massachusetts Institute of Technology’s Robert Langer, ScD, and Xiaolei Yin, PhD, Karp discovered two key pathways that, when activated, trigger stem cells in the intestinal tract to replicate and remain as stem cells. The research team developed two drugs that activated these same pathways, causing the cells to proliferate.

Intestinal stem cells have similar properties to the progenitor cells in the inner ear that give rise to hair cells. “When we subjected progenitor cells in the inner ear to our small molecule drugs, these once-dormant cells came back to life,” said Karp, who cofounded Frequency Therapeutics to rapidly advance these small molecule drugs to clinical trials. The company just completed a Phase I/II trial for hearing restoration.

Pursuing “Bioinspiration”

In his 2015 TEDMED Talk, Karp describes how his lab uses solutions found in nature to develop medical tools, treatments and technologies. Known as “bioinspiration,” his lab’s observations of geckos, snails, slugs, jellyfish and parasites have led to breakthrough technologies and multiple consumer products, transforming fields such as tissue adhesives, regenerative medicine and drug delivery.

For example, the Karp lab’s study of slugs and snails inspired a biodegradable adhesive that can be used as glue to seal leaks in a human heart. In 2017, Gecko Biomedical’s sealant product received European approval as a medical device for vascular reconstruction.

“Before we embark on a research project, we always employ what I call ‘radical simplicity.’ This involves spending a considerable amount of time defining and deconstructing a problem to make sure the potential solution will be as simple as possible,” Karp said.

This “radical simplicity” philosophy involves thinking about details such as manufacturing, clinical trial design, insurance reimbursement and regulatory strategy. Considering these hurdles early maximizes the potential of bringing a technology to the clinic. Karp gave a TEDx Talk about radical simplicity at the John F. Kennedy Presidential Library and Museum.

“Ultimately, our goal is to bring technology to patients as quickly as we can,” said Karp.

The research on hair cell regeneration is quickly advancing and may one day yield a therapy to restore hearing in humans. Karp adds that this is also a new paradigm — a druggable, tissue-regeneration platform. Dormant progenitor cells exist in the eyes, brain, liver, muscles and cartilage, so there are potentially innumerable applications for these small molecules beyond hearing loss. “This is just the beginning,” he said.

More details about the Karp lab can be found on the team’s website.