Study discovers an oral bacterial connection to Alzheimer’s progression

A new study claims that an oral bacterium advances the progression of Alzheimer’s disease or AD. Alzheimer’s is degenerative disease, a progressive form of dementia, and eats away at the brain of people susceptible to the gene.

Many genetic, lifestyle and environmental factors cause Alzheimer’s. However, the study found an unlikely perpetrator: the Porphyromonas gingivalis (Pg) bacterium, which thrives in the mouths of those suffering from chronic gum disease.

Significant Findings Of Oral Bacteria-Alzheimer’s Study

The study with unexpected results was published by the privately held, clinical-stage pharmaceutical company, Cortexyme Inc. in collaboration with many international scientists in ‘Science Advances.’ However, according to researcher Jan Potempa at the University of Louisville and Department of Oral Immunology and Infectious Diseases in the School of Dentistry, the evidence doesn’t amount to proof. While these pathogens were found in progressing Alzheimer’s brains, they couldn’t conclusively be held responsible for the advancement of the disease.

Nevertheless, Potempa expresses support for the discovery, and said, “We now have strong evidence connecting P. gingivalis and Alzheimer’s pathogenesis, but more research needs to be done before P. gingivalis is explicitly implicated in the causation or morbidity of AD. An even more notable aspect of this study is the demonstration of the potential for a class of molecule therapies targeting major virulence factors to change the trajectory of AD, which seems to be epidemiologically and clinically associated with periodontitis,” reported Science Daily website.

When the theory was tested in animals, the researchers found that the infection causing Porphyromonas gingivalis bacteria also established colonies in their brain, and the bacteria increased production of amyloid beta (Aβ). The heightened Aβ production causes amyloid plaque, which has been frequently linked to Alzheimer’s disease.

Another significant finding of the study includes the detection of toxic organism enzymes named gingipains, which are solely secreted and transported to the neurons via the outer bacterial membrane surfaces. These gingipains interact with the neurons and affect two significant protein markers—tau protein (responsible for normal neuronal function) and ubiquitin protein (responsible for tagging damaged protein chains).

Cortexyme Designs New Alzheimer’s Medicine

Based on their findings, Cortexyme sought to block the neurotoxicity caused by Porphyromonas gingivalis bacterium. The company attempted to conceive a series of small molecule therapies targeting specific Pg bacterial enzymes. Before the clinical trials began, the researchers had stated the basic foundation of their experiment by demonstrating the reduction in Pg bacterial load by merely suppressing the COR388 compound, which also blocked the Aβ42 production leading to significant reduction in neural inflammation.

All these steps had the combined effect of protecting the neurons in the hippocampus. The hippocampus is the complex neural structure of the brain’s grey matter and is responsible for emotions, motivation, and the formation and storage of memories. It is generally the first to atrophy when one acquires Alzheimer’s disease.

Once the first phase of the clinical trials proceeded in expectedly, Cortexyme made their outcome public in October 2018 at the 11th Clinical Trials in Alzheimer’s disease Conference. Their phase 1b trials successfully showed how COR388 suppression caused AD patients to perform better in cognitive tests. On the basis of this success, Cortexyme plans to start Phase 2 and 3 clinical trials of COR388 in 2019.