LL-37 Peptide

One family, one member. Humans make a single cathelicidin and this is the whole roster.

LL-37 is a 37 amino acid cationic peptide and the only cathelicidin produced by humans, released by proteinase 3 from the 170 residue precursor hCAP18 and acting on bacterial membranes through charge based disruption. Its clinical candidate form ropocamptide failed a phase 2b trial, the sponsor was subsequently liquidated, and the compound has been flagged by the FDA.

Some animals carry a dozen of these. Cows have a small library. Pigs have several.

Humans make one.

It does not start life as LL-37. It gets cut out of a larger precursor protein called hCAP18 by an enzyme, proteinase 3, and the 37 residues that come off are the active part.

So the name is literal in a way names in this field usually are not. Two leucines at the start, thirty-seven residues long. Somebody named it after what it looks like on paper.

A cationic peptide that your own neutrophils are releasing right now, sold here as a research material, and studied almost entirely on skin rather than anywhere else.

It punches holes in membranes and it also talks to your cells. Two jobs, one peptide.

Look, most antimicrobial peptides do one thing and it is a fairly blunt thing. They are positively charged, bacterial membranes are negatively charged, and physics does the rest.

LL-37 does that. It also does something considerably more interesting.

That dual character is why it turns up in immunology papers and dermatology papers and cancer-biology papers, which is a strange spread for a molecule this small.

The research that reached clinic went at epithelial migration, which is why the trial work sat on skin rather than anywhere systemic.

Here's the honest part. A molecule that does two different things is harder to develop, not easier, because now you have two mechanisms and two sets of consequences.

Everything clinical here has been topical. Not injection, not systemic administration, and the distinction is not a technicality.

The trial exists, it was well run, and it did not deliver. All three matter.

There is a real trial here, it was properly run, and it is worth reading rather than summarising.

Mahlapuu and colleagues, 2021. The HEAL LL-37 trial: 148 patients, phase IIb, double-blind, three arms, fifteen sites in Poland.

Read that carefully, because it is the useful kind of negative. A well-designed trial that reports honestly is worth more than three positive papers with fifteen animals each.

There is one other trial on the record, NCT02225366 at MD Anderson, which went in a completely different direction and is not about the same question at all.

So the file is: strong basic science, one good clinical trial that did not deliver, and a lot of internet enthusiasm that has not caught up with either.

We would rather tell you the trial did not work than hope you never look it up.

Same day out of British Columbia. Our building, our cold packs, our people, and nothing sitting in a customs queue while you refresh a tracking page.

Then into the fridge. Keep it cold and keep it dark. Sealed and freeze-dried it handles a rough trip without ice. Once it lands, fridge.

FDA has published a concern. Cathelicidin LL-37 sits on the FDA list of bulk drug substances that may present significant safety risks, in the withdrawn-nomination section. FDA cites nonclinical findings suggesting detrimental effects on male reproduction and that the substance can be protumorigenic in some tissues. We would rather you read that here than not at all.