Wednesday, 21 August, 2019


Gum disease bug linked to Alzheimer’s (and new drug is being tested)

Gum disease bug linked to Alzheimer’s (and new drug is being tested) Gum disease bug linked to Alzheimer’s (and new drug is being tested)
Patty Aguilar | 25 January, 2019, 23:59

They also studied the enzyme's effects in the brains of mice, and found that it caused the animals to develop signs of Alzheimer's. "I'm fully on board with the idea that this microbe could be a contributing factor".

Referring to tau, a protein associated with Alzheimer's disease, Dominy told Newsweek: "Studies reported in our paper indicate that P. gingivalis and gingipains can directly kill neurons, damage tau, elevate levels of beta amyloid, and increase markers of neuroinflammation".

The study also showed that sleep disruption rapidly spreads Tau while it also causes the release of synuclein protein which leads to Parkinson's disease.

The research team, which is coordinated by pharma startup Cortexyme that was co-founded by first author Stephen Dominy, isn't claiming to have discovered definitive evidence of Alzheimer's causation. Yet. At the time, he was treating people with HIV at the University of California, San Francisco.

Professor Colin Masters AO from the Florey Institute said, "The blood test accurately predicted when members of a family with inherited Alzheimer's disease would begin to show symptoms".

"Our identification of gingipain antigens in the brains of individuals with AD and also with AD pathology but no diagnosis of dementia argues that brain infection with P. gingivalis is not a result of poor dental care following the onset of dementia or a outcome of late-stage disease, but is an early event that can explain the pathology found in middle-aged individuals before cognitive decline", the authors write in their paper. "He points out that while most of the data presented in the Cortexyme study supported their hypothesis, gingipains weren't found in all of the Alzheimer's-affected brains, 'so whilst it may be a cause, the data don't exactly support it being the only cause".

Previous research has shown options for detecting Alzheimer's disease in its early stages. That early appearance is important, Lynch says, because "you would expect it to be there before the onset" of symptoms.

However, he said the study was limited because the team has not yet determined if different strains of P. gingivalis are more virulent than others in causing brain infection. Giving mice a gingipain-inhibiting substance by mouth twice a day treated the brain infection and was better at reducing bacterial load than the antibiotic moxifloxacin (a recommended treatment for people with gingivitis).

Seeking to block Pg-driven neurotoxicity, Cortexyme set out to design a series of small molecule therapies targeting Pg gingipains.

A drug developed by the company, COR38, is now in human trials. A larger study is slated to start this year.

We don't know for sure that P. gingivalis causes Alzheimer's disease in humans, or that the drug will work.

They tested the saliva and cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, of people with Alzheimer's disease, looking for presence of P. gingivalis DNA. "These are odd ideas, but they seem to be getting some traction".

Following this, scientists tested drugs in mice aimed at blocking the toxic proteins and found they were able to halt degeneration in the brain.

Tau is normally found in the brain - even in healthy people - but under certain conditions it can clump together into tangles that injure nearby tissue and presage cognitive decline. "It really will be important to see how this plays out in human randomized controlled trials, which is the gold standard for understanding whether a therapeutic targeting something like the P. gingivalis mechanism would actually be effective", she said. But he's skeptical that the bacteria or its toxin directly cause Alzheimer's.

In other words, it's unknown whether gum disease increases the risk of Alzheimer's or if people with dementia have an increased risk of gum disease because of poor oral care.

Understanding that process has revealed potential drug targets, she said, since repressive histone modification is controlled or catalyzed by enzymes. Inherited Alzheimer's is rare genetic disease. Not necessarily. But if healthy people want to stay on the safe side and potentially reduce their risk, Noble says, "the main conclusion we still have is: brush and floss".

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