[Heidi L]

(one more try to explain this without confusing so many people)

It's commonly known that a severe allergy to peanuts can cause death within minutes.
What if there were an allergy that disabled people slowly, over their entire lifetime?
That's what I believe is happening in many cases of Parkinson's disease.

Celiac disease is an allergy to gliadin, a specific gluten protein found in grains such as wheat, barley and rye. In celiac disease the IgA antigliadin antibody is produced after ingestion of gluten. It attacks the gluten, but also mistakenly binds to and creates an immune reaction in the cells of the small intestine causing severe damage. There is another form of gluten intolerance, Dermatitis Herpetiformis, in which the IgA antigliadin bind to proteins in the skin, causing blisters, itching and pain. This can occur without any signs of intestinal damage. Non-celiac gluten sensitivity is a similar autoimmune reaction to gliadin, however it usually involves the IgG form of the antibody and damage to the small intestine is not common.

It has recently been shown that certain IgG antigliadins can bind to proteins in the brain.
I believe this starts a process which causes the cumulative brain damage seen in PD.

This is some of the data which started my research:
-IgG class antibodies were found bound to dopamine neurons and Lewy bodies in brains from Parkinson's patients indicating an immune reaction.
-Idiopathic PD is significantly associated with HLA antigen gene DQB1*0602.
-HLA DQB1*06 alleles are also associated with Non-celiac gluten sensitivity. In fact DQB1*06 alleles seem to confer a higher risk to present neurological rather than intestinal symptoms.


This is the process I have proposed:
1. Genetically susceptible people produce antigliadin antibodies capable of binding to brain proteins. These antibodies are ordinarily too large to pass through the blood-brain-barrier, and no damage occurs.
2. The BBB is compromised somehow. This may be due to age-related degradation or trauma or chemical exposure. The blood-brain-barrier has been found to be more porous in Parkinson's patients than in control subjects.
3. Antibodies slowly begin to infiltrate the brain, attack the neurons, and obstruct neurotransmitter release. This causes an excess of alpha-synuclein in the cell and initiates the formation of lewy bodies. These accumulated products kill the cells over time, reducing dopamine levels further until symptoms become apparent.
4. Over time, degradation of the BBB accumulates and progression of the disease accelerates. There are also many reports of sudden onset or rapid progression after trauma or chemical exposure.

I believe this mechanism is also valid for persons with Parkin mutations. It seems they are less able to process the alpha-synuclein after is has accumulated.

(I have a paper detailing this mechanism with references posted on my website. For the record, I have narcolepsy which I believe is an acute, early manifestation of the same process.)

Let me stress, these antibodies do not have any affinity for the intestine.
However, each person can create up to four different versions of the antigen which produces this antibody (two protein chains x two sets of alleles=four products), Therefore you may also produce a form which does damage the intestine. You may also have other genes which produce celiac disease.
There is no reason to expect any correlation between gastrological symptoms and your risk of neurological damage due to gluten sensitivity.

Anyhow, if you are interested here is a list of some non-intestinal symptoms of GS which you or one of your relatives may exhibit: migraines, sleep disorders, defective tooth enamel, chronic mouth sores, over or under-active thyroid. Intestinal diseases associated with GS include: irritable bowel syndrome, Crohn's disease and diverticulitis.

Personally I believe that anyone with PD symptoms in the absence of proven manganese toxicity should be tested for gluten sensitivity. However I have not been able to convince even one person with PD yet. I have sent my paper to every major organization and any practitioner I have felt might be interested, yet have received no indication anyone is taking it seriously. I feel that they are all too beholden to their own interests to consider a preventative treatment which involves one test and no drugs at all. Of course I realize this isn't a cure for those who are already affected, but I do believe gluten avoidance can halt further progression of the disease. (In addition to myself, I do already have reports from 5 narcoleptics of positive tests, or rapid remission of their symptoms on a gluten-free diet.)

Celiac tests are specific for intestinal tissue antibodies and usually do NOT include an assay for IgG antigliadin. There are specific tests for gluten sensitivity which do include IgA and IgG antibodies. Your doctor may agree to order one for you, but as far as I can tell, most of them aren't aware of, or open to the possibility of neurological effects of gluten.

There are two US labs where you can order your own test:

ImmunoLabs Anti-Gliadin Antibody Assay (2 tests, IgA and IgG) $132
This one requires going to a local lab for a blood draw and the serum gets mailed to them.
Some people who are gluten sensitive do test negative via blood though.

Enterolab Fecal test for Gluten sensitivity. $99
This requires a sample that you mail back to them. It is the most sensitive and accurate test available.

If you are elsewhere, let me know, I'll find one for you too.

Thanks for reading, I'm sorry this was so long, but I really believe this is a valid possibility which should be investigated. I will continue to pester the medical research community until I'm either proven right or wrong.

-Heidi

For more information on the neurological effects of gluten, please see The Gluten File
For my story and hypothesis, see my website linked to my profile.

[indigogo]

Heidi - your hypothesis makes just as much sense to me as others, meaning, why not? I'm willing to talk to my neuro about it, and see if she'll order a test. If not, then I can do it myself. No harm done, and it would be interesting because I don't have the gastrointestinal symptoms. The role of alpha-synuclein is much discussed; the mechanism unknown. I think you are right about people not paying attention because of varying reasons for their own self-interest.

[Ronhutton]

Heidi,
We have had a lot of discussion on this, and it seems to me this is basically a futher example of my ideas on the role of the BBB.
If a person has a defective BBB, he is susceptible to toxins entering the brain, and this is one example of the possible toxins. If the BBB is not defective, you agree he will not show PD symptoms.

"These antibodies are ordinarily too large to pass through the blood-brain-barrier, and no damage occurs.
The BBB is compromised somehow. This may be due to age-related degradation or trauma or chemical exposure."

So a defective BBB is the key requirement to cause PD, not gluton sensitivity. I have a friend with celiac disease, and he certainly does not show any PD symptoms.
Other sources of damaging toxins have been identified, eg helicobacter pilori, but 50% of the population have this bacteria, but only the ones with a defective BBB get PD.

Back on my hobbyhorse of the defective BBB, remember that the permeability is variable. Stress causes a sudden widening with all the increase in symptoms that we know well. when the stress has passed, the BBB recovers somewhat, and our symptoms subside somewhat also. However, the BBB ages with time and becomes steadily less efficient, explaining why PD is largely an older person's disease.
I pointed out that the BBB would get to a permeability where dopamine could leak out of the brain into the bloodstream, once a critical permeability was reached. Also, I postulated carbidopa could leak in! This would prevent your brain being able to convert levodopa into dopamine.
A recent report confirms carbidopa can do exactly this.
http://www.ihop-net.org/UniPub/iHOP/...l?pmid=2753115
So carbidopa, like gluten and many other toxins can enter the brain and cause PD symptoms, but the overriding requirement is a defective BBB.
Ron

[indigogo]

Ron - we know that damaged dopamine neurons play a role in PD, but we don't know yet what damages those neurons. Couldn't gluten sensitivity be one answer? How do we know unless we ask the question? How can it be ruled out unless tested?

Or are you saying that it really doesn't matter what is doing the damage - the more important question is how do we fix a damaged/leaky BBB?

[paula_w]

Now we are talking about two things but I don't think they have to be unrelated.

Ron, a researcher conversationally told one of our members that she believed the GDNF trial participants that developed antibodies did so because it leaked back out of the blood brain barrier.

Heidi, I wouldn't give up. Your theory makes a lot of sense and i have many gastrointestinal symptoms and stomach pain from certain foods. Always have had right side pain from certain foods or activities.

paula

[Heidi L]

Oh, I'm not giving up.
Ron and I have been discussing this. I agree with him that certain things can widen the BBB at times, and that this allows more toxin (antibodies!) into the brain. But I would argue that the symptomatic ups and downs are much more easily explained by varying levels of antibodies in the blood.
One of my "side theories" is that narcoleptics have a much more permeable membrane. I can correlate my ups and downs directly to what I eat, down to the hour.

Carey has convinced me to go to the Seattle conference next week and I will pester some of the researchers up close and in-person.

[Heidi L]

For the record, I am pretty sure my BBB still has big fat holes in it, and I am asymptomatic since giving up gluten.

And my overwhelming stress response, which I believe is related to impaired suppression of the vagus nerve, has disappeared.

Ron, it's gotta be a this AND that. There's also people with BBB damage who don't have PD or N.

[Ronhutton]

Carey,
Yes, I am suggesting that the BBB is the thing to concentrate on. Find a way to reduce the permeability and that will stop a lot of toxins getting in, like those proposed by Heidi, or toxins from helicobacter, or many other types, which circulate harmlessly in the blood stream of a healthy person. Possibly the symptoms of PD vary so much because it depends which toxin has succeeded in getting past the BBB.
I am certainly not saying Heidi is not correct in her proposal. Rather I am saying it is another example of a different toxins which get through a compromised BBB. However, if you have a sensitivity to gluten, and a defective BBB, you will show PD symptoms. If you don't have a defective BBB, only gluten sensitivity, you won't show PD symptoms.
The ideas proposed by Heidi are linked with a defective BBB therefore, but I don't want to divert the thread to the BBB, so I will open a new thread and summarise what I think. I believe the main test of any theory is it has to have answers for all questions and facts.
Heidi,
Yes, I agree, it has to be this and that, but the this is always a defective BBB. For example a defective BBB and gluten sensitivity. A defective BBB and toxins from helicobacter, a defective BBB and toxins from a virus, and so on. As I have said, your ideas are certainly not wrong, but it does need a defective BBB as well.
Prof Leenders found each of the PD people he examined all had a defective BBB. Have you got a reference to people with a damaged BBB not showing PD? It is of course possible to have mild damage to the BBB below the threshold needed to cause trouble and the first signs of PD.

Ron

[aftermathman]

would your "permeated bbb" theory not also be potentially relevant for other neurodegens, e.g. Alzheimer's, and have you had any joy discussing this with specialists in those fields ?

Neil.

[Heidi L]

Ron, People with MS have BBB damage that is strongly correlated to herpes virus infection.

Aftermathman, I agree about the alzheimers. It's got to be similar, just a different pathological catalyst. I suspect it's also something ubiquitous and therefore going unnoticed. But no, I haven't even been able to get traction on this hypothesis yet, however if it's right I'm sure the rest will follow.

I've been itching to post this somewhere, it's been running through my head lately:
"There is a game of puzzles," he resumed, "which is played upon a map. One party playing requires another to find a given word --the name of town, river, state or empire-any word, in short, upon the motley and perplexed surface of the chart. A novice in the game generally seeks to embarrass his opponents by giving them the most minutely lettered names; but the adept selects such words as stretch, in large characters, from one end of the chart to the other." -E.A.Poe, The Purloined Letter