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. 2022 Oct;31(10):987-993.
doi: 10.1080/13543784.2022.2117605. Epub 2022 Sep 1.

COR388 (atuzaginstat): an investigational gingipain inhibitor for the treatment of Alzheimer disease

Marwan N Sabbagh  1 , Boris Decourt  2
Affiliations

COR388 (atuzaginstat): an investigational gingipain inhibitor for the treatment of Alzheimer disease

Marwan N Sabbagh et al. Expert Opin Investig Drugs. 2022 Oct.

Abstract

Introduction: Evidence from in vitro and in vivo studies demonstrates that amyloid beta (Aβ) oligomers have potent, broad-spectrum antimicrobial properties created by fibrils that entrap pathogens and disrupt their membranes. Data suggest that Aβ may play a protective role in the innate immune response to microbial infections and that Aβ in the brain plays a damaging role when the inflammatory response is not well controlled.

Areas covered: This paper describes the relationship between periodontal disease and Alzheimer disease (AD), the role of Porphyromonas gingivalis and its secreted gingipains in AD, and the potential of the gingipain inhibitor atuzaginstat (COR388) to modulate AD neuropathologies.

Expert opinion: P. gingivalis is opsonized by Aβ42, is capable of entering the brain, and is an accelerant of neuropathologies in rodent models of AD. Thus, in our opinion, this bacteria is highly likely to be a pathogen capable of initiating or precipitating the progression of AD, which agrees with the pathogen hypothesis of clinical AD development.

Keywords: Alzheimer disease; Porphyromonas gingivalis; atuzaginstat; clinical trials; gingipain; neuroinflammation; periodontal disease.

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Conflict of interest statement

Declaration of interest

M Sabbagh discloses ownership interest (stock or stock options) in NeuroTau, Inc., Optimal Cognitive Health Company, uMETHOD, Athira Pharma, Inc., and Cognoptix, Inc.; consulting for Alzheon, Inc., Biogen Idec, GmbH, Cortexyme, Inc., Genentech (Roche Group), Acadia Pharmaceuticals, Inc., T3D Therapeutics, Inc., Eisai Co., Ltd., Eli Lilly and Co., and KeifeRx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. Proposed mechanistic targets of atuzaginstat.
Used with permission from Cortexyme, San Francisco, California.
See this image and copyright information in PMC

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