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.
Reference:
