Retraction notice: 'The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System' and related Wright/Harding lab Dihexa publications
Journal of Pharmacology and Experimental Therapeutics (editorial)
Journal of Pharmacology and Experimental Therapeutics (2025)
April 2025 retraction notices removed two of the key Wright/Harding lab mechanism papers for Dihexa — Benoist 2014 on HGF/c-Met dependence and Kawas 2012 on AngIV analog development — following research-integrity investigations. The McCoy 2013 foundational paper has been under an expression of concern since 2021. The mechanism case for Dihexa is now substantially weaker than the public peptide-vendor literature acknowledges.
This entry exists to ensure the corpus represents the Dihexa evidence accurately, because the public peptide-vendor literature substantially overstates the mechanism case after the post-2021 retractions and expressions of concern affecting the Wright/Harding lab at Washington State University. The retraction notices published in April 2025 in the Journal of Pharmacology and Experimental Therapeutics removed two of the lab's most-cited Dihexa-relevant papers: (1) Benoist et al. 2014 ("The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System," originally J Pharmacol Exp Ther 351(2):390-402), which had been the principal mechanism citation for the HGF/c-Met-binding story; and (2) Kawas et al. 2012 ("Development of Angiotensin IV Analogs as Hepatocyte Growth Factor/Met Modifiers," originally J Pharmacol Exp Ther 340:539-548), which had been a key chemistry-and-pharmacology paper for the analog series. Both retractions followed a multi-year investigation that began with a 2021 expression of concern on four papers and that intersected with the Leen Kawas / Athira Pharma image-manipulation matter (Kawas was forced to take leave from Athira after Washington State's investigation into figure-data alterations; Athira's CEO transition and subsequent regulatory communications reflected the investigation outcome). The McCoy et al. 2013 paper — the foundational Dihexa-design-and-characterization paper that this site separately catalogs and that has been the most-cited public source on Dihexa's pharmacology — was placed under an expression of concern in September 2021 (J Pharmacol Exp Ther 378(3):313) and has not been formally retracted as of May 2026, but it sits on the same research-integrity track as the now-retracted papers.
Retraction and expression-of-concern do not categorically mean the underlying scientific claims are false; they mean the data record cannot be relied on as published. In particular, the HGF/c-Met-modulator mechanism story has independent partial corroboration from Athira's fosgonimeton clinical-development program (see Hua 2022 entry on this site), although the LIFT-AD Phase II/III failure in 2025 weakens the clinical-validation arm of that corroboration. Dihexa as a discrete chemical entity has its in-vivo and ex-vivo behavior characterized primarily by Wright/Harding lab outputs, and there is no independent replication of the original cognitive-restoration findings by a separately funded laboratory using a separately synthesized batch of compound — a structural gap in the literature that the retractions have made acutely visible. This entry takes no position on the personal-conduct aspects of the underlying investigation and is offered solely as an evidence-quality note for the platform's readers. The expression of concern on McCoy 2013 does not invalidate that paper; the existing McCoy 2013 entry on this site is retained, but readers should weigh it against the broader retraction context that this entry documents.
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