Porphyromonas gingivalis is the pathogen responsible for chronic periodontitis (CP) or gingivitis. A prospective observational study of patients with Alzheimer’s disease (AD) and active CP showed a notable decline in cognition (Alzheimer’s Disease Assessment Scale-Cognitive and Mini Mental State Examination scales) during a six month period compared to AD patients without active CP.
P. gingivalis is an assachariotic gram-negative anaerobic bacterium that produces major virulence factors known as gingipains. These are cysteine proteases consisting of lysine-gingipain (Kgp). These gingipains play critical roles, arginine-gingipain A (RgpA) and arginine gingipain B (Rgp B). These gingipains play critical roles in host colonization, inactivation of host defenses, nutrient acquisition and tissue destruction.
A team of scientists from Cortexyme inc. and their colleagues from around the world hypothesized that P. gingivalis infection acts in AD pathogenesis through the secretion of gingipains to promote neuronal damage. Their studies in sex and age matched brain tissue cores from both AD patients and neurologically normal individuals showed that 96% of AD samples were positive for RgpB and 91% of AD samples were positive for Kgp. Both were significantly higher than the levels in non AD control brain samples. In addition to the presence of gingipains, P.gingivalis DNA has been shown to be present in the cerebrospinal fluid (CSF) of clinical AD patients.
The team has identified three small molecule gingipain inhibitors. The first two, COR286 and COR271 are irreversible inhibitors and have IC50 values less than 50 pM. And a third molecule COR119 is a reversible inhibitor with an IC50 of 10 nM. At the cellular level both COR286 and COR271 protected cells infected with P.gingivalis in a dose dependent manner. More impressive was the observation that COR271 which has oral bioavailability and significant CNS penetration was successful in reducing the bacterial load in the brains of mice previously infected with P.gingivalis
While this research is both promising and exciting, take care of you teeth and gums. Should you have gingivitis get it treated as aggressively as possible.
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