With human bodies being bags of mostly salty water and countless messy biochemical processes, it’s little wonder that over time some residues tend to collect in these systems. Although evolution has seen fit to also evolve a range of mechanisms to clean up many of those messes, some of these waste products are left to gather, such as advanced glycation end-products (AGEs). Implicated in everything from diabetes to chronic kidney disease and general aging-related conditions, recently researchers have developed a way to break down one type of these AGEs.

Called N(6)-Carboxymethyllysine (CML), there is evidence to suggest that the presence of AGEs like it in the extracellular matrix (ECM) has damaging effects on the ECM’s functioning, as observed in e.g. the inhibiting of collagen crosslinking and the resulting ‘aging’ of skin among other tissues. Essentially these waste product jam up the normal biochemical machinery, while also triggering pro-inflammatory factors.

Beyond aging-related conditions, this can result in a whole range of other diseases that may be resolved if these waste products could be cleaned out. To this end [Narisa Trabosh] et al. of the San Francisco-based Revel Pharmaceuticals laboratory created CMLase, an enzyme that breaks down CML.

The challenge here was to design this enzyme, which used a genetic selection approach in modified E. coli to narrow down suitable enzymes, optimized for dealing with free CML. Once they were fairly confident that they had a working enzyme, they had to test it and observe the results.

This testing was performed in model proteins in vitro, as well as in tissue samples from elderly donors. These latter included lens, skin and arterial tissue, all of which are long-lived tissues that have plenty of time to collect CML. After treatment with CMLase the presence of CML in these tissues was reduced by 55% for skin and 75% for arterial tissue.

Of course, as also noted in the article these are ex vivo experiments that do not yet directly translate to living patients. An initial human trial would need to show safety above all, even if the amount of waste produced by the clean-up of CML won’t be that significant.

Subsequent trials would need to demonstrate that such removal of CML leads to healthier tissues, which if confirmed would open the path for other pathogenic AGEs to get their own matching enzyme.