ArticlePharmacology research & perspectives2020
Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.
Article in Pharmacology research & perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Gingipain inhibitors as an innovative therapy for periodontal and associated-systemic diseases: a systematic review.Clinical oral investigations · 2025Pooled it
- Porphyromonas gingivalis Outer Membrane Vesicles-Associated DNA Triggers Inflammation by Inducing IL-6 in Astrocytes.Molecular oral microbiology · 2026Article
- Oral-Systemic Links: A Narrative Review of the Role of Periodontitis in Alzheimer's Disease Development.Cureus · 2026Review
- Bidirectional relationship between the biofilm ofMicrobiology spectrum · 2026Article
- Review
- Assessment of periodontitis vaccine using three different bacterial outer membrane vesicles in canine model.mSphere · 2025Article
- Exploring heme and iron acquisition strategies of Porphyromonas gingivalis-current facts and hypotheses.FEMS microbiology reviews · 2025Review
- Article
- A review of the roles of pathogens in Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Longitudinal Analysis of Canine Oral Microbiome Using Whole Genome Sequencing in Aging Companion Dogs.Animals : an open access journal from MDPI · 2023Article
- Paradigm Shift: Multiple Potential Pathways to Neurodegenerative Dementia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- [Developments in Research on the Relationship BetweenSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Review
- Article
- Oral frailty and neurodegeneration in Alzheimer's disease.Neural regeneration research · 2021Review
- Multi-pathogen infections and Alzheimer's disease.Microbial cell factories · 2021Review
- Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.Neuropsychiatric disease and treatment · 2021Review
- Mucosal Vaccination Against Periodontal Disease: Current Status and Opportunities.Frontiers in immunology · 2021Review
- The Use of Antimicrobial and Antiviral Drugs in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.Pharmacology research & perspectives · 2020Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans.
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