Discovery of a bacterial pathogen in the brain of patients with Alzheimer's disease

A new science reveals that an unlikely culprit, Porphyromonas gingivalis (Pg) – the bacterium commonly badociated with chronic gum disease – appears to be at the root of the pathology of Alzheimer's disease.

An article published today in Science Advances details how researchers have identified Pg in the brains of patients with AD.

Jan Potempa, Ph.D., a researcher at the University of Louisville, Ph.D., Department of Oral Immunology and Infectious Diseases of the School of Dentistry, was part of the 39 team of international scientists led by Cortexyme Inc., a private clinical stage pharmaceutical company.

According to Potempa, although infectious agents have been implicated in the development and progression of Alzheimer's disease, the evidence for the cause is not convincing.

However, "we now have strong evidence linking the pathogenesis of P. gingivalis and Alzheimer's, but further research is required before P. gingivalis is explicitly implicated in the causality or morbidity of AD. .

"An even more remarkable aspect of this study is the demonstration of the potential of a clbad of molecular therapies targeting major virulence factors to alter the trajectory of AD, which appears to be badociated epidemiologically and clinically with periodontitis," he said. said Potempa.

In animal models, oral infection with Pg resulted in colonization of the brain and increased production of beta-amyloid (Aβ), a component of amyloid plaques commonly badociated with AD.

The research team also discovered the body's toxic enzymes, or gingipains, in the neurons of patients with AD. Gingipaines are secreted and transported to outer bacterial membrane surfaces and these substances have been shown to be responsible for the toxicity of Pg in various cells. The team correlated gingipain levels with a pathology related to two markers: tau, a protein needed for normal neuronal function, and ubiquitin, a small protein label that marks damaged proteins.

In an attempt to block Pg-induced neurotoxicity, Cortexine began designing a series of small molecule therapies targeting gingipain Pg. In preclinical experiments detailed in the article, the researchers demonstrated that inhibiting the COR388 compound, there was a reduced bacterial burden related to a Pg-established brain infection, a blocked production of Aβ42, reduced neuroinflammation and protected neurons in the hippocampus – the part of the brain that governs memory and atrophy frequently at the beginning of AD development.

In October 2018, Cortexyme announced the results of its Phase 1b clinical trial on COR388 at the 11th Alzheimer's Disease Clinical Trials Conference. COR388 has shown positive trends in several cognitive tests in patients with AD and Cortexyme plans to initiate a phase 2 and 3 clinical trial of COR388 in mild-to-moderate AD in 2019.

Source: University of Louisville