Very revealing: “Recent research has shown that the APOE gene may play a larger role than previously believed in Alzheimer’s disease development, suggesting that a solid understanding of APOE is important to a comprehensive hypothesis of Alzheimer’s causation,” said Casey Lynch, Cortexyme’s chief executive officer, co-founder, and chair, and a co-author of today’s presentation. “We believe the data presented today provide insight into why APOE4 increases the risk for Alzheimer’s disease: the ApoE4 protein, which is important for synaptic maintenance and control of neuroinflammation, has a higher propensity to be fragmented by gingipains, compared to other forms of ApoE. Importantly, our human studies have shown the ability of COR388 to protect ApoE proteins from gingipain fragmentation in the brains of study subjects.”
A growing body of evidence points to P. gingivalis as playing a key role in the development of Alzheimer’s disease given its identification in the brains of AD patients and its ability to cause neurodegeneration, inflammation, beta-amyloid and tau buildup, and other pathology associated with the disease in animal models. An asacchrolytic bacterium, P. gingivalis has been shown to infiltrate the brain and release toxic proteases called gingipains that cleave ApoE, tau, and other proteins associated with neuronal function. Cortexyme is developing COR388, an investigational small-molecule gingipain inhibitor that is currently in a large, international Phase 2/3 clinical trial (the GAIN Trial). This trial is evaluating the efficacy, safety, and tolerability of COR388 in patients with mild to moderate AD, with top-line results expected in the fourth quarter of 2021.
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