Elevated N-acyl taurines mark rapid ALS progression and identify FAAH inhibitor PF-04457845 as survival-extending agent in mice
Plasma NAT elevation tracks faster ALS progression; the FAAH inhibitor PF-04457845 slows motor neuron loss and extends survival in mice by modulating microglial state. The work bridges human metabolomics with iPS and animal validation but remains preclinical. Larger cohorts and early human trials are the required next steps.
Limitations include modest cohort size for the metabolite screen, reliance on a single genetic mouse model, and absence of direct NAT quantification after drug dosing in vivo. Larger longitudinal patient collections are required to test whether baseline or serial NAT levels predict clinical course or pharmacodynamic response. Planned work will evaluate additional endocannabinoid-modulating agents and move PF-04457845 toward investigator-initiated early-phase testing if biomarker validation holds.
Katsuno group: NAT levels will stratify 12-month survival with >70% accuracy in an independent 80-patient ALS cohort measured within 24 months.
Sources (2)
- [1]Primary Source(https://insight.jci.org/articles/view/186123)
- [2]Supporting Source(https://pubmed.ncbi.nlm.nih.gov/36811953)