Cortexyme (CRTX -0.5%) announces encouraging preclinical data on lead candidate atuzaginstat (COR388) that, it says, support its potential for treating cardiovascular disease (CVD) and Alzheimer’s disease (AD). The data are being presented at the Alzheimer’s Association International Conference.
The company says the results demonstrate the role of a bacterium called Porphyromonas gingivalis (P. gingivalis) in both CVD and AD and provide a possible explanation for why the two often occur together.
P. gingivalis, a oral pathogen believed to effect more than half of adults that causes gum disease (gingivitis), releases toxic enzymes called gingipains. A preclinical study in a rabbit model of atherosclerosis (buildup of plaques in arteries) showed that oral infection with P. gingivalis accelerated atherosclerosis while treatment with atuzaginstat, a gingipain inhibitor, reduced inflammation and the formation of unstable atherosclerotic plaques.
P. gingivalis releases gingipains when it invades the brain. Results from nerve cell cultures showed that atuzaginstat and proprietary gingipain inhibitors protected neurons infected with the bacterium from synapse loss while reducing bacterial load in infected neurons, astrocytes and microglia and protecting against deficits in other pathways impacted by the pathogen.
A Phase 2/3 clinical trial, GAIN, assessing atuzaginstat in patients with mild-to-moderate AD dementia, is ongoing with an estimated completion date in December 2022.
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