Study published in Nature Communications describes CMLase, an engineered enzyme that reverses a form of protein damage long considered permanent

Shows that structural damage in human tissue can potentially be reversed

Revel Pharmaceuticals today announced a study published by its scientists as well as researchers at Calico and the University of Colorado Anschutz Medical Campus, in Nature Communications. The paper describes CMLase, an engineered enzyme that reverses a stable form of chemical damage that builds up in long-lived proteins over decades.

The damage, known as Nε-carboxymethyl-lysine (CML), is a type of advanced glycation end product ("AGE"). It forms when sugars react with proteins in a process similar to the browning reaction that turns bread into toast. In the body this reaction unfolds slowly over a lifetime, altering proteins in skin, blood vessels, and other tissues.

Using directed evolution across more than 500 million enzyme variants, the Revel team engineered CMLase from a bacterial glycine oxidase scaffold. Tested on human tissue from donors ranging in age from 20 to 75 years old, the enzyme reduced CML levels by more than 70% in a 75-year-old donor's arterial tissue and by more than 55% in aged donor skin, bringing CML levels in the skin samples below those typically seen in 31-year-old skin. The enzyme also repaired the majority of damage sites across various model proteins, all while leaving the underlying proteins intact.

"This class of damage has been seen as a fixed part of aging since the 1980s," said Aaron Cravens, corresponding author and CEO, Revel Pharmaceuticals. "What we've shown is that CML damage in human tissue can, in fact, be reversed under laboratory conditions. More work is needed, but these results alter the starting assumption for how we think about this fundamental aspect of the aging process."

The article may be accessed online at: https://www.doi.org/10.1038/s41467-026-75141-2

About Revel Pharmaceuticals

Revel Pharmaceuticals is a biotechnology company developing engineered enzymes to reverse structural damage associated with aging. Using directed evolution, Revel's platform aims to reverse accumulated crystals, as well as oxidative and glycation damage in aging tissues. The company’s research is supported in part by Small Business Innovation Research (SBIR) grants from the National Institutes of Health (NIH). Revel is Headquartered in San Francisco, California.

https://revelpharmaceuticals.com

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"What we've shown is that CML damage in human tissue can, in fact, be reversed under laboratory conditions," said Aaron Cravens, corresponding author and CEO, Revel Pharmaceuticals.