Researchers at Revel Pharmaceuticals have engineered CMLase, an enzyme that breaks down N(6)-Carboxymethyllysine (CML), a glycation end-product that accumulates in long-lived human tissues and drives aging-related pathology in everything from skin to arteries to diabetic kidneys. In ex vivo tests on tissue from elderly donors, CMLase reduced CML presence by 55% in skin and 75% in arterial tissue. The work, led by Narisa Trabosh et al. and published in Nature Communications 2026, represents the first targeted enzymatic clearance of this specific AGE from human tissue samples.
The enzyme was developed using genetic selection in modified E. coli, screening candidates optimized for free CML. CML accumulates in the extracellular matrix, where it disrupts collagen crosslinking and triggers pro-inflammatory signaling. The paper details how that selection process was narrowed down, validated first in model proteins in vitro, then in lens, skin, and arterial tissue from elderly donors. That methodological chain is worth reading in full.
No human trials exist yet. The immediate next step is a safety-focused Phase 1 study. If CMLase clears that bar and subsequent trials confirm tissue health improvements, the authors propose that other pathogenic AGEs could each get their own matched enzyme, turning this into a platform rather than a single therapeutic.
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