Is This Under-the-Radar Stock Set to Succeed in Alzheimer's Disease?

[Jmac]

A promising new approach could potentially yield a new drug providing hope for millions of Alzheimer's patients worldwide.
...Fighting Alzheimer's disease from a new angle
In recent years, scientific evidence forged a link between P. gingivalis infection, more commonly known as gingivitis, and Alzheimer's disease. The scientific thesis for Cortexyme's approach focuses on the discovery that the P. gingivalis bacteria can enter the bloodstream and make its way to the brain, particularly in older individuals and those with a genetic predisposition. Once inside brain cells, also called neurons, the bacteria release a toxic substance called gingipains. The gingipains digest neuronal proteins leading to the death of the brain cell...
https://www.fool.com/investing/2020/02/ ... in-al.aspx

I really, really need to get off my butt and go see my dentist. Not the first time I've read something about this one, probably saw it on this forum

[Family Tree Guy]

Hi Jmac-
I follow this one pretty closely and I am really hoping that when they announce results of their clinical trial at the end of 2021, it is good news for all of us. The interesting twist to this 'gingipain hypothesis' of AD is that it completely explains why E4s are so heavily hit by AD. The APOE gene makes protein that differs slightly whether you are E2,3, or 4. The protein made by E2 has no arginines, the protein made by E3 has one arginine, and the E4 protein has two arginines. In all other regards the proteins are identical. This bacteria Pg is asacrolytic, meaning that instead of consuming carbohydrates it chews up proteins. The enzyme that Pg secretes to accomplish this task, is called gingipain and guess what-- it selectively chomps on the arginine portion of the apolipoprotein made by the APOE gene. So the fragments caused when the gingipain chomps on the arginine completely muck up the brain. So basically the bacteria does much more damage if you are E4, and there are way more clumps if 4/4. At least that's the theory...

The drug being tested here works when regular (wild type) mice were deliberately infected with Pg. (The Pg induced AD like symptoms, then the drug fixed them). This is very different than most animal AD studies which used genetically engineered mice which over expresse a-beta. The Ph 1 study was safe, but only had a few patients for about a month, so hard to draw many conclusions for efficacy. Regular anti-biotics won't work here because they tend to target dividing, growing bacteria. Pg tends to lie dormant and thus evades traditional anti-biotics.
Best regards,
-FTG

[circular]

Hi Jmac-
I follow this one pretty closely ...

Wow, that was interesting. Thanks for sharing it.

[DebbieG]

I follow this one pretty closely and I am really hoping that when they announce results of their clinical trial at the end of 2021, it is good news for all of us. The interesting twist to this 'gingipain hypothesis' of AD is that it completely explains why E4s are so heavily hit by AD...

Family Tree Guy,
Do you know about the gingipain bacteria lifespan once they take up residence in the brain? If gingivitis is treated effectively and these bacteria are no longer entering the brain, will the ones already in the brain die off at some point?
Thanks for the information.
Debbie

[Family Tree Guy]

Debbie-
from what is known, I believe the answer to your question is no. There is no evidence whatsoever that Pg, once in the brain, while 'die off'. To be fair, the presence of Pg in the brain has not been all that widely studied until very recently. Based on what we know of other microbes dwelling in the brain, Pg likely persists for decades. It is not even clear to me that really serious gum disease is required for Pg to get into the bloodstream and make its way to the brain (but by all means everyone should get good dental care).

The scientific literature is full of a wide variety of micro-organisms that dwell in the brain of both apparently healthy and diseased brains. I speculate that we could imagine a healthy brain having some level of equilibrium amongst all these bugs, and that something happens to cause Pg to get more active and start causing havoc. (It could be advanced age or other co-factors... and perhaps many of our lifestyle interventions like exercise, nutrition, stress reduction, etc. help to maintain the equilibrium)

Last year there was a fascinating and very clearly written article published on the 'Beehive Theory' of traumatic brain injury that I would recommend to anyone interested:
https://www.sciencedirect.com/science/a ... 7719302129
The idea is that knocking your head stirs up all the micro-organisms in your head in the same way swatting a beehive with a stick stirs up the residents of hive.
best,
FTG

[Family Tree Guy]

A couple additional comments on this subject:

1) The gingipain theory appeals to me because it potentially explains a true root cause of AD that I have not seen in other explanations. In particular, the amyloid theory that the past ~300 drug failures have been based has never made sense to me from first principles. If molecular biology is the story of how a gene makes a protein, and we know that APOE4 (especially 4/4) so dramatically raises AD probability, then it seems logical to me that the actual protein expressed by the E4 gene must play a key role in the disease progression. Amyloid is part of the innate immune system and I have not seen any clear explanation why having E4 gene directly triggers excess Amyloid plaques. That is, amyloid is a response to something, not a direct product of a particular allele you posess...

2) All of that said, an understanding of the true root cause of AD may not be necessary to find fixes. Medical history has a few wonderful examples of solutions without true understanding (example: Jenner implemented a very effective 'vaccination' type solution to smallpox ~50 years before Pasteur even described his germ theory of medicine). The most elegant example of this approach right now may be the gene therapy approach described on some other threads here where E4 carriers could be treated with a virus to swap out the E4 for a E2. It might end up working even though it sheds no real insight into what E4 is 'doing' to instigate AD.

[BarbaraS]

Hi Jmac,

I've taken to using an an old ayurvedic technique called oil pulling to prevent some or all of p Gingavilis from entering my brain. I swish organic coconut oil -- which reduces gum inflammation and gingivalis -- with a drop or two of oil of oregano (another bacteria fighter) -- for up to 10 minutes every morning. This practice does such a great job at this as well as completely eliminating plaque and tartar that my dental hygienist has almost nothing to do because my teeth and gums are so squeaky clean.

I continue to look for other organic and herb/plant-based options and will report back on what I find.

BarbaraS

[Jmac]

Hi Jmac,

I've taken to using an an old ayurvedic technique called oil pulling to prevent some or all of p Gingavilis from entering my brain. I swish organic coconut oil -- which reduces gum inflammation and gingivalis -- with a drop or two of oil of oregano (another bacteria fighter) -- for up to 10 minutes every morning. This practice does such a great job at this as well as completely eliminating plaque and tartar that my dental hygienist has almost nothing to do because my teeth and gums are so squeaky clean.

I continue to look for other organic and herb/plant-based options and will report back on what I find.

BarbaraS

I am doing the same except I use MCT oil rather than coconut, mainly because I couldn't make myself do the gunky coconut oil I add oregano oil and have just ordered myrrh, clove, cinnamon and peppermint oils to add to the mix, they should be here today. I did some research on things to cut back on tooth and gum issues, those were touted by some so I figure why not?

[CarrieS]

Hi Jmac,
I am doing the same except I use MCT oil rather than coconut, mainly because I couldn't make myself do the gunky coconut oil I add oregano oil and have just ordered myrrh, clove, cinnamon and peppermint oils to add to the mix, they should be here today. I did some research on things to cut back on tooth and gum issues, those were touted by some so I figure why not?

I've been oil pulling with coconut oil for years and like the idea of adding these essential oils. Seems like a great aromatic way to start the day! Thanks for posting the ideas!

[circular]

Is anyone worried about killing off healthy organisms in the mouth this way? Absent signs of PG, is this like throwing antibiotics into a healthy gut? That asked, I saw something the other day about antibiotics helping dementia symptoms. I think that’s discussed in the forum.