Cortexyme Presents Data Supporting Role of P. Gingivalis in Alzheimer’s Pathology at Advances in Alzheimer’s and Parkinson’s Therapies Virtual Focus Meeting 2020
-- New results demonstrate P. gingivalis’ ability to infect neurons and cause characteristic Alzheimer’s pathology
-- Cortexyme’s lead compound, COR388, targets gingipains produced by P. gingivalis and is currently under investigation in the Phase 2/3 GAIN Trial
“Over the past several years,
P. gingivalis is best known in published literature as the keystone pathogen in the development of periodontal disease. P. gingivalis produces toxic virulence factors known as gingipains, and previous research from
The research presented at AAT-AD/PD investigates changes induced by P. gingivalis at the cellular level. The data shows the expression of P. gingivalis and gingipains inside of co-cultured brain cells after infection, including neurons, astrocytes, and microglial cells and the display of cellular pathology consistent with AD. This outcome reinforces the findings of previous research on the impact of P. gingivalis in the in vivo biological environment of the central nervous system. It also provides support for the premise of Cortexyme’s ongoing GAIN Trial studying the efficacy of COR388, a gingipain inhibitor, in improving downstream pathology of the bacterium and alleviating AD symptoms.
“The Phase 2/3 GAIN Trial of COR388 is supported by years of research that the neurodegeneration associated with Alzheimer’s may be caused by a bacterium and the gingipains it releases within the central nervous system,” said
To view the poster, please visit the Presentations page under the News & Events heading of the
About the Research Presented at AAT-AD/PD
In the study, infected neurons displayed AD-like neuropathology, including accumulation of autophagic vacuoles and multivesicular bodies, the same structures found in dystrophic, or dysfunctional, neurites in AD brains. The neuron cultures also demonstrated cell loss, tau phosphorylation, neurofilament changes, and a significant loss of synapse density after infection with P. gingivalis, mirroring the changes seen in AD brains.
The neuron-astrocyte-microglia co-culture model also allowed researchers to observe that, in infected cultures, P. gingivalis was taken up by microglia, where it caused increases in Il-6, Il-8, TNFα and Il-1β cytokines, notable markers of inflammation, signaling an inflammatory immune response similar to that seen in the Alzheimer’s-affected brain. At the same time, researchers saw reduced levels of Trem-2, a microglia-secreted protein, and ApoE, a known gingipain substrate, in these infected cultures.
The results from this in vitro model reinforce the results of previous in vivo studies of P. gingivalis, demonstrating that the pathogen is able to infiltrate the central nervous system and provide support for the role of P. gingivalis in inducing AD pathology.
About the GAIN Trial
The GAIN (GingipAIN Inhibitor for Treatment of Alzheimer’s Disease) Trial is a randomized, double-blind, placebo-controlled Phase 2/3 trial is evaluating the efficacy, safety, and tolerability of COR388, Cortexyme’s investigational gingipain inhibitor, in patients with mild to moderate Alzheimer’s disease. The GAIN Trial also includes a sub-study measuring the efficacy of COR388 on symptoms of periodontal disease including gingival pocket depth. The GAIN Trial has been ongoing since the second quarter of 2019, with top-line results expected in the fourth quarter of 2021. For more information on the trial, visit www.gaintrial.com.
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