Given that human bodies are primarily composed of salty water and involved in numerous complex biochemical processes, it’s not surprising that residues can accumulate over time. While evolution has provided various mechanisms for cleaning up some of these messes, certain waste products, like advanced glycation end-products (AGEs), remain. AGEs are linked to issues such as diabetes, chronic kidney disease, and other age-related conditions. Recently, researchers have made progress in breaking down one specific type of these AGEs.
This particular waste product, known as N(6)-Carboxymethyllysine (CML), appears to harm the extracellular matrix (ECM), disrupting its normal functions. For instance, its presence can inhibit collagen crosslinking, contributing to the aging of skin and other tissues. Essentially, these waste products clog the biochemical machinery and trigger inflammatory responses.
Inevitably, the accumulation of these products potentially leads to numerous diseases. If they can be eliminated, it could resolve various related health issues. To tackle this, a team led by Narisa Trabosh from Revel Pharmaceuticals in San Francisco has developed CMLase, an enzyme that effectively breaks down CML.
Creating this enzyme posed some challenges. The team used a genetic selection method in modified E. coli to identify suitable enzymes optimized for handling free CML. After they were relatively sure they had a functional enzyme, they moved on to testing and observing its effects.
This testing involved model proteins in vitro and tissue samples from older donors, including skin, lens, and arterial tissues. These are all tissues that have had ample time to accumulate CML. After treatment with CMLase, the levels of CML decreased by 55% in skin and an impressive 75% in arterial tissues.
However, it’s crucial to note that these are ex vivo experiments, which don’t yet directly apply to living patients. The initial human trials would primarily need to ensure safety—though the volume of waste resulting from the cleanup shouldn’t be overly significant.
Future trials would have to confirm that removing CML genuinely leads to healthier tissues. If successful, this could pave the way for developing enzymes targeting other harmful AGEs.
