toastmasterbone
Registered User
[moved from the meme thread]
I think it's more compelling than that, on first glance. I read the article yesterday in Science Advances (the original peer-reviewed thing), and I rethought my choice of Mike&Ike candies and went to go floss. Later, I ate the Mile&Ike's, but flossed again. I'm now a bleeding mess.
So the article is reporting on the preclinical (animal model) studies in mice, and pilot study in humans, telling us several interesting things:
+ they show the connection between bacteremia of P. gingivalis and Alzheimer's disease (AD) - P. gingivalis secretes a protease (aptly named "gingipain") that degrades cytokines (notably through the gingipain proteases Kgp and RgpA/B, which "are essential for P. gingivalis survival and pathogenicity, playing critical roles in host colonization, inactivation of host defenses, iron and nutrient acquisition, and tissue destruction").
+Researchers found that a diagnosis of AD has a very strong correlation with the amount of gingipain in the brain. Additionally, they found that gingipain was also found in the cerebrospinal fluid (CSF) - they did a pilot study in 10 patients with mild to moderate AD and were able to quantify P. gingivalis DNA in 7/10 samples; they were then able to match these findings to patient saliva (so that testing can be done through saliva rather than CSF or, you know... brain tissue). Patients without a diagnosis of AD (the control group) did not have detectable P. gingivalis DNA in their saliva.
+ Researchers gathered some mice (otherwise known as medical heroes to mankind) and after a a battery of tests, confirmation tests, and validation tests. Researchers came up with small-molecule gingipain inhibitors (ie, the investigational drug), and gave some to 1 group of mice. Another group had no treatment. All mice were then given an injection of Kgp and RgpB into their wee little brains, and a week later, their brains were analyzed for neurodegeneration. The control group had a significant number of degenerating neurons; the treatment group had nuthin', The treatment blocked neurodegeneration.
+ Researchers did a bazillion more studies like this.
+ Researchers took their orally bioavailable, brain-penetrant Kgp inhibitor into clinical trials, and are currently testing in patients with AD. The hope is that based on the mouse data, that treatment "will reduce P. gingivalis infection in the brain and slow or prevent further neurodegeneration and accumulation of pathology in AD patients."
Take away message:
+ I don't know what Phase (1, 2, or 3) of development they're in. Phase 1 is really early, just a fact-finding mission, really, in a small number of patients. Phase 2 has a larger number of patients with AD, and if the results (and the risk/benefit is good), then on to Phase 3 in a larger group of patients, and that's the last Phase before approval. If Phase 2 is successful, the FDA might start talking about fast-tracking the vaccine for approval as they push through Phase 3.
+ I've worked on several studies where the results of animal models looked amazing, but didn't do so well in humans.
+ All in all, the preclinical testing looks crazy good for validation of a correlation of gingivitis to AD; the preclinical results in mice looks really promising for an oral vaccine.
+ Time will tell.
I eagerly await your book on the subject.
Would also love to hear anything you know about the gingivitis / Alzheimer's link.
There is some (not definitive) evidence that Alzheimer's is associated with a bacterial infection. So, gingivitis may be a pathogens way of entering the body and then contributing to an increased risk of Alzheimer's.
I think it's more compelling than that, on first glance. I read the article yesterday in Science Advances (the original peer-reviewed thing), and I rethought my choice of Mike&Ike candies and went to go floss. Later, I ate the Mile&Ike's, but flossed again. I'm now a bleeding mess.
So the article is reporting on the preclinical (animal model) studies in mice, and pilot study in humans, telling us several interesting things:
+ they show the connection between bacteremia of P. gingivalis and Alzheimer's disease (AD) - P. gingivalis secretes a protease (aptly named "gingipain") that degrades cytokines (notably through the gingipain proteases Kgp and RgpA/B, which "are essential for P. gingivalis survival and pathogenicity, playing critical roles in host colonization, inactivation of host defenses, iron and nutrient acquisition, and tissue destruction").
+Researchers found that a diagnosis of AD has a very strong correlation with the amount of gingipain in the brain. Additionally, they found that gingipain was also found in the cerebrospinal fluid (CSF) - they did a pilot study in 10 patients with mild to moderate AD and were able to quantify P. gingivalis DNA in 7/10 samples; they were then able to match these findings to patient saliva (so that testing can be done through saliva rather than CSF or, you know... brain tissue). Patients without a diagnosis of AD (the control group) did not have detectable P. gingivalis DNA in their saliva.
+ Researchers gathered some mice (otherwise known as medical heroes to mankind) and after a a battery of tests, confirmation tests, and validation tests. Researchers came up with small-molecule gingipain inhibitors (ie, the investigational drug), and gave some to 1 group of mice. Another group had no treatment. All mice were then given an injection of Kgp and RgpB into their wee little brains, and a week later, their brains were analyzed for neurodegeneration. The control group had a significant number of degenerating neurons; the treatment group had nuthin', The treatment blocked neurodegeneration.
+ Researchers did a bazillion more studies like this.
+ Researchers took their orally bioavailable, brain-penetrant Kgp inhibitor into clinical trials, and are currently testing in patients with AD. The hope is that based on the mouse data, that treatment "will reduce P. gingivalis infection in the brain and slow or prevent further neurodegeneration and accumulation of pathology in AD patients."
Take away message:
+ I don't know what Phase (1, 2, or 3) of development they're in. Phase 1 is really early, just a fact-finding mission, really, in a small number of patients. Phase 2 has a larger number of patients with AD, and if the results (and the risk/benefit is good), then on to Phase 3 in a larger group of patients, and that's the last Phase before approval. If Phase 2 is successful, the FDA might start talking about fast-tracking the vaccine for approval as they push through Phase 3.
+ I've worked on several studies where the results of animal models looked amazing, but didn't do so well in humans.
+ All in all, the preclinical testing looks crazy good for validation of a correlation of gingivitis to AD; the preclinical results in mice looks really promising for an oral vaccine.
+ Time will tell.