May 7, 2020
Cortexyme today announced the publication of research further documenting the ability of the pathogen Porphyromonas gingivalis to invade neurons and trigger Alzheimer’s-like neuropathology. This paper was published in the Journal of Alzheimer’s disease. Although P. Gingivalis is best known as a primary driver of chronic periodontal disease, it is also known that it can infiltrate the brain, where it can cause characteristics similar to AD. P. gingivalis breaks down proteins for its primary source of energy by utilizing toxic virulence factor proteases known as gingipains.
More than 90% of post-mortem brains of patients with AD showed a presence of gingipains. Further, in animal models, P. gingivalis results in brain infection and classic AD pathology. In this paper, Cortexyme proofs for the first time that P. gingivalis can indeed invade the human brain and can persist in mature human neurons expressing active gingipains and that these infected neurons show signs of AD-like neuropathology, such as synapse loss.
The paper by Cortexyme strengthens the connection between P. gingivalis and AD, and is thus a gateway to emphasize the importance of therapeutics targeting the pathogen. Cortexyme is developing COR388, an oral administered bacterial protease inhibitor for AD, which is currently in phase 2/3 in the US and Europe. COR388 inhibits gingipains and therefore protects neurons from bacterial toxicity, lower neuro-inflammation and reduces Aβ42 production, thereby preventing further cognitive decline and dysfunction. Results of these trials are expected in H1 2022.