Cortexyme, Inc. (NASDAQ:CRTX), a clinical stage biopharmaceutical company pioneering a novel disease-modifying therapeutic approach to treat Alzheimer’s and other degenerative diseases, today announced the publication of new data in Pharmacology Research and Perspectives revealing further detail about the pharmacodynamics and utility of the company’s lead investigational medicine, COR388. The data provides additional evidence on the ability of COR388 to engage its target, the toxic proteases, or gingipains, released by the bacterium P. gingivalis and the closely related species P. gulae, resulting in beneficial effects on bacterial load and symptoms.
Cortexyme’s foundational research previously identified gingipains in more than 90% of Alzheimer’s disease brains studied. P. gingivalis is best known for its role as a keystone bacterium in the development of periodontal disease, and has recently been shown in animal studies to infiltrate the brain after oral infection and trigger pathology of Alzheimer’s including neurodegeneration, inflammation, beta-amyloid and tau pathology.
In this publication, researchers report that COR388 demonstrates dose-dependent gingipain target engagement in a naturally occurring P. gulae infection, including in difficult to reach bacterial biofilm niches. P. gulae is the only other bacterial species known to secrete gingipains. COR388 was efficacious in improving downstream pathology of the infection, namely gingival pocket depth, a symptom of periodontal disease which affects approximately 65 million Americans. In addition, gingipain antigens and P. gulae DNA were found in the brains of aged dogs, indicating that P. gulae can also migrate from the oral cavity to the brain in a manner similar to that seen for P. gingivalis in Alzheimer’s patients.
“Chronic periodontal disease is common in dogs and, as they age, these animals can experience cognitive decline in much the same way humans do,” said Stephen Dominy, M.D., Cortexyme’s Chief Scientific Officer, Co-founder and co-author on the paper. “This research shows that natural P. gulae infection in canines provides an important model for the study of P. gingivalis infection in humans and emphasizes the ability of this infection to promote degenerative disease in different organs. It also underscores that the anti-gingipain activity of COR388 is effective at reducing bacterial load and has beneficial effects on downstream disease.”
“To change the trajectory of the Alzheimer’s epidemic, we need to move upstream and target the root causes of pathology and cell death,” said Casey Lynch, Cortexyme’s Chief Executive Officer, Co-founder, and Chair. “This paper adds to the growing body of evidence supporting the gingipain hypothesis, the efficacy of COR388 in multiple indications, and the design of the GAIN Trial.”
View the Pharmacology Research & Perspectives paper, “Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388,” here: https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.562