Autoimmune explained
 

Many here have commented on PD being an autoimmune disease...
I didn't really understand what that meant, so have been doing some looking into things.

Here is a roughly 10-minute video of Dr. Trevor Marshall discussing autoimmunity: http://www.youtube.com/watch?v=hcAVeKobsxU

It is very interesting because it goes hand in hand with several observations one can make simply by reading comments and anecdotes from PWP:

different symptoms for each person with some similarity
severity of symptoms different for each person
consistent reports of symptom improvement with use of antibiotic (for other, non-PD reason like infected tooth, etc.)
why drugs do not cure us or even stop progression
why we get worse (pathogen is becoming more prevalent, weakening the body)
why, given the "inponderable complexity" of the interaction of the many pathogens in even healthy people, pills will never be the path to recovery

We are seriously looking into Dr. Marshall's protocol, it may seem complicated but really is not. It is, however, long-term and that in itself is daunting. Has anyone tried it and if so, what happened? There are lots of positive reports for it working for people with other conditions, but I have not been able to find any anecdotes of anyone using it for PD. Please share if you have any experience with this.

I repeat myself
 

Thanks for posting on PANDAS and autoimmunity.
We have discussed these hypotheses several times here and it seems like we can connect PD, infection, inflammation and autoimmunity very well. For those of you interested in this topic, here I go again.

Immunologists use the phrase “Molecular Mimicry” to connect infections with the onset of autoimmune diseases.
Check out Molecular Mimicry http://www.direct-ms.org/molecularmimicry.html for an excellent explanation.

PD fits into this paradigm as well as any autoimmune disorder. If anyone is interested in digging deeper, send me a mail.

“The concept of molecular mimicry is simple but entails a lot of understanding of the workings of the immune system. Basically molecular mimicry means that part of a molecule of a given protein closely resembles a part of another totally different protein.

Proteins are made up of strings of amino acids and in molecular mimicry one series amino acids(eg~10) in one protein is very similar to a string of ten amino acids in another protein. "
To understand how molecular mimicry works in the induction of autoimmunity one must understand the basic mechanisms of an immune responses.

Step 1: What does the immune system see in an infection? When you have an infection, for eg., with influenza virus, your immune system does not look at the whole virus, it recognizes just a part of the protein portion of the invader. It does this with T cells with receptors that bind to short segments(~10 amino acids) of a foreign protein. This short segment of aminoacids is like a name tag or a thumb print of a pathogen.

Step 2: How do you get these small segments of patosgen and what do they do? During an infection, cells called macrophages engulf a foreign invader(eg a bacteria or virus) and break it down into fragments. These fragmented viral antigens are recognized by “T cells” circulating in the body. (It is called antien presentation)

Step 3: What do T cells do? T cells are like good soldiers, they go to the site of infection, make all sorts of cytokines and kill infected cells.

Step 4: How does a T cell recognize infected cell? For T cells, infected cells are those that display the “name tag” (10 amino acid string of the viral protein). If infected cells fail to show their name tag, T cells cannot kill them and vice versa. This is the interesting part. If cells display the name tag, but are not infected and perfectly alright, T cells still attack them and kill them.

Let me put this theory in the context of PD:

Influenza infection generates T cells specific to name tag A
PD onset starts with misfolded proteins (eg., alpha-syn) and neurons try to get rid off it by chopping down (autophagy is the technical term). Defects in this process due to genetic mutations (UCHL-1) do contribute to PD. A combination of defective protein and defective autophagy could lead to generation of small strings of amino acids resembling viral name tag A. Net result is that now neurons are displaying the name tag A, though they are not infected with influenza.
Clumps of alpha-syn also generate neuroinflammation.
T cells notice inflammatory signals and enter brain. There are plenty of neurons displaying name tag A and T cells get busy with cytokines and killing all the “infected cells”.
This is how I see infection, PD and autoimmunity fitting together. There are well established methods to test these hypotheses………….may be some day it would be tested

Girija

odd that this should come up now
 

I would like to add my two cents here as I have been hitting the books on this pretty heavy here of late.

There is also a concept of an "auto-toxic" reaction. A true auto-immune reaction involves antibodies and the more advanced areas of the immune system. Auto-toxic reactions involve the more primitive areas and the microglia. It is a more brute force response without the precision that comes with identifying the enemy and producing a defense just for him. It holds the fort, so to speak, until the special ops guys can get there.

As a result, there can be a lot of collateral damage if this primitive barrage is not shut down as soon as it is no longer needed. But it is essential in those early phases. The problems arise when that primitive defense doesn't shut down properly or reactivates upon minimal stimulus.

Things can get quite deadly. Sepsis is a case of this runaway reaction. The invaders may be long gone but the microglia continue to pour out inflammatory chemicals.

PD seems to be a similar situation. Researchers (Carvey, Liu, Hong, etc) established a decade ago that fetal exposure to chemicals (lipopolysaccharides or LPS) from the maternal immune response could "prime" the offspring's primitive system to be hypervigilant and run for months when shutdown should have been in hours.

This hypervigilant reactivaton seems to be a major factor in PD. And not just because of the physical damage. There are about two dozen different inflammatory chemicals involved and they are very active and alter our behavior in many ways - including producing what we have considered PD symptoms.

We have seen clues to this on this board. Remember Ron Hutton laid low by an infected tooth? The inflammatory response to the tooth triggered the bigger reaction of his own microglia. Then there are those intriguing cases where a PWP reports that an antibiotic for an unrelated infection seemed to erase his PD symptoms so long as he took them. Much to the doctor's amusement. And pretty much ignoring the facts that some antibiotics (tetracyclines and penicillins,in particular) have a property totally unrelated to their effect on bacteria - they are great anti-inflammatories capable of breezing past the BBB and are fat soluble as well and so go deep into the brain. Once there they calm the microglia, the chemistry rights itself, and PD symptoms improve or even disappear!

I have been on the verge of trying one of these (minocycline). I even talked my GP into a month's worth, but I may have found an even better option which I am trying first.

Green tea extract is, well, I have shouted "Eureka!" too many times. Let's just say that the last four days of my life have been very encouraging.

l-form bacteria
 

Thanks for those great posts, although I have to admit being in way over my head here (not that that has ever stopped me before...:).

That said, what I have read of Dr. Marshall's theory thus far is that the problem is l-form bacteria, which actually lack cell walls and so insert themselves inside the cytoplasm of the human's cells. That's why they are so hard to get rid of, they are "stealth" bacteria. To me, this sounds different from the molecular mimicry girija posted about? And if so, then what?

There is much more at curemyTh1.com, I'm still learning about all this so forgive my ignorance.

interview with Luc Montagnier, speaking about infections leading to autism, pd, ms, lyme:

http://www.liloumace.com/Research-up...008_a1833.html

Some concerns...
 

While I am definitely in the infection as trigger for PD camp, I do have some reservations about the theory as it applies to PWP. First, while I think the Marshall Protocol is an interesting manifestation of the theory I am always wary of something touted as a panacea and if you look at the list of illnesses that they attribute to l-form bacteria it is a little over the top. I really think they need to publish more measurable clinical results of the Protocol's efficacy with various diseases.

For those who have PWP, we need to try and establish that this is the right course of treatment for our individual "type" of PD. In other words, rule out genetics especially if you are young onset. I think there is some sort of Vitamin D connection that one must test for to establish candidacy for the Protocol. I am saying make sure the odds are in your favor this can help. I am afraid that the treatment is risky for treating PD based on a case study of a similar treatment for eradicating h. pylori bacterial infections for PWP. A clinical trial shut down because people who had a resistant strain of pylori experienced significant worsening of their PD. While it is not the same thing exactly it is the same principle of the Marshall Protocol and treatment is similar.

http://www.whatsdrivingparkinsons.net/pdf/3.pdf

Oh, and PWP on the MP? I don't think many PWP know of it. Last time I checked out their user forum... they had broached that topic and I think there were only 2 PWP in the Protocol.

Hate to sound like a downer but that worsening thing is scary. While it is part of the Marshall Protocol treatment to worsen, it is only supposed to be temporary as you fight off the bacteria. The h. pylori study alarmed me because it was easy to infer there was a permanent decline in their PD.

Lot's to consider...

Laura

bumping this up
 

considering the discussion concerning inflammation, infections and neutrophils.

http://rationalwiki.org/wiki/Marshall_Protocol

Hi Girija,

This is a link I found ages ago about Polyglandular Autoimmune Endocrine disorders.

It describes 2 syndromes associated. The second mentions PD.


http://www.dundee.ac.uk/medther/taye...yglandular.htm