PE 22-28 preprint on TREK-1 knockout mice - translational gap thoughts

Posted by amber464 in Research & News - 0 points, 1 comments.

Came across a new preprint looking at PE 22-28 in TREK-1 knockout mice versus wild-type. The knockout mice showed baseline antidepressant-like behavior without the peptide, which makes sense mechanistically but complicates the translational story. If the target is already genetically absent, you can't really measure additive effect.

What stood out to me: the dose-response curve in wild-types was surprisingly flat between 10 mcg/kg and 100 mcg/kg ip. No clear saturation in the forced swim test. That either means the assay ceiling is too low or

Comments

• aaron_n: the flat curve is weird. forced swim test has a hard ceiling anyway - mice stop swimming at some point no matter what you give them. did they run a locomotor control to rule out sedation at the high end? also ip dosing in mice does not map cleanly to human subq. the knockout baseline effect is the real tell though. if TREK-1 deletion alone mimics the peptide you are basically looking at a target engagement problem not a dosing problem. i have not touched PE 22-28 myself, mostly stuck to gh pepti

Community discussion - research and educational context only. Not medical advice.