Bloods from both PD and healthy blood samples were analysed using thromboelastography (TEG), confocal and electron microscopies, and for cytokine and other circulating biomarkers. PD and healthy plasma clots were probed with a polyclonal antibody for the bacterial protease, gingipain R1, from P. gingivalis. Low concentrations of recombinant gingipain R1 were also added to purified fluorescent fibrinogen. TEG, fibrin(ogen) amyloid formation and platelet ultrastructure analysis confirmed profound hypercoagulation, while the biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. The authors provide evidence for the presence of the protease, gingipain R1 in PD blood, implicating inflammatory microbial cell wall products in PD.
Parkinson’s disease: a systemic inflammat... - Cure Parkinson's
Parkinson’s disease: a systemic inflammatory disease accompanied by bacterial inflammagens
Thank you Iqbaliqbal. Too bad they do not suggest treatments based upon this view of the disease.
Edit - update:
Having mulled this over, I now I am of the opinion that this result is an effect rather than a cause of Parkinson's. If so, that renders the original comment invalid:
-------
This seems to be a radically new idea about the causation of Parkinson's disease. New to me at any rate. I read the entire paper and did not see anything obviously wrong with it. I plan on taking a look at some of the references also. Be that as it may, if this thesis is correct, the treatment would be an appropriate antibiotic:
ncbi.nlm.nih.gov/pubmed/217...
Antibacterial susceptibility patterns of Porphyromonas gingivalis isolated from chronic periodontitis patients
"Susceptibility testing revealed a sensitivity of 100% of P. gingivalis to azithromycin, doxycycline and amoxicillin/clavulanic acid"
This gets very interesting because doxycycline has been reported to help alleviate Parkinson's. The reasons attributed to this have been other than the antibacterial effect. This thinking may be in error - the reason why it apparently has been effective may be due exactly to its antibacterial effect.
The gingipain theory has been floated for AD; Maxwell Biosciences is working on a therapy for AD based on it. The CEO gave a talk at Undoing Aging, unfortunately it seems as though they only put up a portion of the talk on YouTube (sometimes they edit out slides and stuff since they don't want proprietary information generally distributed):
In the mean time, what has helped me most with gum health:
- Sonicare
- regular flossing
- supplements: CoQ10, PQQ, K2
- cardio training (both the exercise and supps help with microcirculation)
- swishing with green tea
Chicken, egg, I don't know. I don't want rotting gums or neurodegenerative disease or CVD - so why not do what I can...
Try this, using this has cut my gum pockets in half. The hygienist was amazed. FLORASSIST® Oral Hygiene. You can get it from Life Extension.
My gums are doing really well, but thanks for the information on the probiotic. The use of bacteriophages is interesting.
If anyone else is interested, Michael Lustgarten recommends peppermint oil for oral health (interview starts at 4:42):
Seems a very important finding.
Very nice.
Would have been nice if they could talk about treatments, agreed.
Maybe though, from reading the paper, treatment implications for the present moment might include brushing your teeth, of course, and getting to dental hygienist as much as they would have you do, try to keep those gums in good shape. Seems that cause is implicated in some cardiovascular disease already. Where they mention gingiva, that is a gum bacterium, i.e., "gingivitis." Then there are stress-induced causes of systemic inflammation I suppose, don't know much about that but have read a few articles about it.
Another implication is that that the reaction is fueled by immune response of various immunoglobulins (these particular here being those involved in clot formations, with a further hypothesis being that the amyloid-beta and alpha-synuclein pathologies being involved as cellular detritus that our trash-consuming and -clearing capabilities can't keep up with or break down for transport out of the cell.
Unfortunately, it also implies that as we keep as a society abusing anti-biotics (the latest being USDA allowing growers of oranges and grapefruits in Florida and California to use vast quantities of two anti-biotic groups to stop some kind of blight on their crops recently), this E.coli might become more resistant to what are left of the current anti-biotic crop, as several pharmaceuticals have recently mentioned that it is no longer a cost-effective prospect to pursue new anti-biotic development.
So what is left on Xeno's question is maybe: while we wait for new anti-biotic treatments to start looking more appealing to develop (there is some work looking at gene-splicing and CRSPR gene editing), the most immediate answer for us is: try like heck to avoid low-grade, seemingly symptomless systemic infections in the first place (keep your teeth and gums up to date, gingivitis is what they are basically talking about in this study but then some logic would suggest other places creating systemic infection or inflammation like GI disorders, and maybe stress disorders -- does anyone know whether those are real, I've never studied them).
And maybe the other hope is to look for or hope for researchers developing immunoglobulin-cancelling immune suppression, like the several dozen or so high-dollar treatments for various immune illnesses now do (anything with "mab" and "ib" at the end of its generic name are basically very specific immune blockers). Like Humira and a large and growing bunch of others, humira targets a certain specific anti-body, as that whole class of new drugs does).
This was a very good grab by Iqbal!
re: treatments
The video I linked to above is a presentation by the CEO of Maxwell Biosciences; they are developing a broadly antimicrobial drug that is a mimetic of human cathelicidin antimicrobial peptide LL-37.
Another strategy is to inhibit the activity of gingipains; some natural product inhibitors exist, among them green tea, cranberry extract, and lactoferrin:
ncbi.nlm.nih.gov/pmc/articl...
~
re: stress
Cortisol increases growth of P. gingivalis:
ncbi.nlm.nih.gov/pubmed/242...
~
Of course the gingipain theory of dementia as presented in the video leaves me with a question - if amyloid is 'good', then why are people with Down's Syndrome at such high risk for developing early onset AD ?
{Sorry for the italics, the editor keeps putting it in and I have no idea why and I don't have time to bother with getting rid of it}
Whoever said amyloid is good? Amyloid is very, very bad. Has somebody been smoking their sox?
See video at 3:57. Amyloid is ' good' in that amyloid is part of an anti-pathogen response, and it has been suggested that it is only a problem if clearance is too slow because clearance mechanisms are impaired or there is a high level of overproduction and the clearance mechanisms are overwhelmed (and I suppose the overproduction angle is the answer to my Down Syndrome question; I'm having a lot of brain farts lately, probably to do with lack of sleep).
makes a lot of sense to me .. I feel my PD gets a lot worse if I have a cold , I have always felt this is no coincidence as regards inflammation ... but I am cautious of antibiotics imo they can cause a lot of damage
Inflammation can wreak havoc in the body! Think about arthritis flare-ups, for example. I do believe that inflammation plays a role, in the Parkinson's Disease process. It is good that researchers are delving into this aspect, of Parkinson's Disease!
DIET seems to be a major contributor to reducing PD severity
Someone posted a study where antibiotics were use for Parkinson's (maybe Alzheimer's?) With success. I couldn't understand why. Now with this study, it makes more sense.
Somewhere back somewhere I mentioned where there was some clinical data on people who had H1N1, I think, and a variant of the Spanish Flu that swept the world about 100 years ago that is still around today, what they noticed was vast swaths of cells that produce dopamine and a few other cell areas obliterated like a clear-cut forest.
Ah, I see just below Felix has already addressed it.
It is indeed a very interesting publication. Here are few interesting facts regarding bacterial or viral (enteroviruses are my personal favorite f1000research.com/articles/... ) nature of the PD:
1. Enteroviruses are often unique to particular species (humans in this case) which would explain why PD is not found in animals.
2. There was at least one study done at Cambridge that proved that viruses have "particular appetite" for very specific cells in the brain, for example substantia nigra.
3. There were several studies that point to increased production of alpha synucleins as a protective reaction against virus infection. Moreover misfolding of ASNs was demonstrated in infected cells in one of the studies.
4. Enteroviruses live (exist is more proper term) in the gut. There are numerous articles that correlate changes in the gut flora composition with the changes in the enterovirus population. Hypothesising that this is the cause of the changes in gut microbiome observed in PD doesn't seem to be unreasonable.
5. Cell organelles implicated in PD (endoplasmic reticulum for example) are the same organelles used by viruses to take over the cell function. This is particularly true for RNA viruses like enteroviruses.
6. There are numerous chronic neurodegenerative illnesses tired to enteroviruses. One good example would be polio. An interesting fact: prior to vaccine discovery virus infections with polio enterovirus were very common but only a very small percentage of people (1%) developed polio. Is it due to genetic link making some people immune system less likely to repel viral infection?
I could continue this list and I also could provide the links to the articles I mentioned above. My main goal here is to point the potential high scientific value of this work. One more PD trivia fact: 4 other members of MJ Fox crew contracted Parkinson at the same time as he did (intmath.com/blog/environmen... ) . What are the odds?
I tried to talk to MJFox foundation and Parkinson foundation about setting up "targeted research" funding with the goal of 1. Replicating findings of the British researchers possibly in a blind study, 2. Isolating pathogenic virus and sequencing it. No takers. I wonder if talking to research institutions in countries where this research can be done cheaper (China, Russia, India) would yield better results
"I also could provide the links to the articles I mentioned"
Yes please! No. 2 is of particular interest to me. Thanks.
Hi Felix,
Is your offer to provide links still open?
I am particularly interested in the last part of No. 3. i.e. "Moreover misfolding of ASNs was demonstrated in infected cells in one of the studies."
Thanks,
Jeff
Or possibly if you have apathy with your PD you can’t be bothered with oral hygiene so the gingivitis develops? Which causes which ?
Gingivitis is but one of numerous forms of what they call systemic low grade inflammation from various sorts of infections and stress...back to cortisol over-production and immune system turning around and attacking normal cells because immune cells are basically killers and cause mayhem like a road accident, which then has to be cleared and the road rebuilt or patched up, all of which then also has to be cleared, and it never is the same either after that, and more damage collects sooner unless entirely rebuilt...think of it as potholes in your body bits...then all that resulting trash, it must go into the landfill, pay for the materials, expertise, labor, all of which is a serious expense and eventually eats away at the city road budget...same impact on the body, contributes to the general wearing out and oxidation (remember a few years back when the world discovered what "free radicals" and "oxidative stress" and other bleaching damage to cells?) Eventually things get worn down or die. Aging, it is.
Low grade stresses and systemic fevers, like you might have with small infections of the mouth as a chronic thing, without real noticeable systems, takes you down sooner, in general, and into specific areas too...it's like putting bleach in your blood and letting it distribute all over your body, where it basically does what bleach does to everything, puts holes in your cells, in the organelles in your cells, kills them and you slowly. Too many "reactive oxygen species" free electrons reach out and strip out pieces of the structures they pass near by to. Turns you into a zombie over time...before your time. You just wear out and eventually die. So the idea is to try to combat that. My cardiologist says more people get heart disease and make it worse because they don't brush their teeth enough...and I myself am a lifelong offender, even though I definitely know better, so I'm not trying to be holy about anything.
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