We have talked here often about the best theory being the one that answers the most questions (again, thank you Ron!). I'm throwing this out there in light of recent posts and discussions about MB and welcome any and all comments.

I'm beginning to think PD, Alz., and maybe even others are caused by pathogens, we dont' even know which one. To think we know all of the virus, bacteria, fungii, pathogen, on the planet is beyond arrogant. We don't, and even if we did, they mutate! So to me, it is entirely possible that there could be some stealth pathogen (or more than one, maybe you have XYZ pathogen, someone else has ABC) that invades us, maybe in our youth, maybe shortly before symptoms appear, that resides in our body and ultimately causes a neurological condition. Here's why.

1. we know PD "spreads" to healthy neurons (healthy stem cells were implanted in Canadian PWP and years later, on autopsy, they discovered the healthy cells had succombed to the same fate...we also progress...if it did not spread, I dont' think we would get worse over time).

I dont' think this is because a cell dies and the surrounding cells cannot communicate with it any more. I doubt very seriously that our neurons function like a strand of Christmas lights, the old ones, where if one went out, the entire remaining strand went dark as well. Rather, I think our neurons are like stars, with multiple connections, and if one goes out, the network has sufficient other connections with each other to keep functioning, until so many are lost that you have a problem. Comments?

2. Several folks have reported their symptoms disappear or radically improve when taking antibiotics. Why would this happen? I appreciate that antibiotics may reduce inflammation, which would help, but aspirin does that, as well as NSAIDS. So there must be something there at play besides just the inflammation angle.

3. There is the rather huge outbreak of PD in the 1900s, right after the flu pandemic, which points to something like this. I think the PD outbreak was actually far worse but diagnoses was much less precise then and of course no internet so folks not in large cities may not have even been aware of it.

4. As was pointed out to me by one researcher, PD is more common on farms. We posture that this may be because of the high use of pesticides (perhaps) and/or well water, but this researcher mentioned to me that he found it significant that farmers are exposed to far more "earth-borne pathogens" than most, with multiple times more potential for infection (cutting, bruising, hurting yourself while tending to farm chores). I have farmers in my family and I can tell you that yes, there are constant cuts, abrasions, openings in the skin where an opportunistic pathogen could get in.

5. Now for inflammation. That has to play a role, I think, and perhaps it is this. Maybe you get a pathogen in you, and it lies dorman like herpes, perhaps for years. It may even come and go, as in herpes: we all know stress triggers herpes fever blisters, so this makes sense.

But then, kabam, life hits you with major stresses....Rick has posted of several, we all have had them. When you are stressed significantly, the immune system gets compromised. At that time, the pathogen has the opportunity to really get busy and replicate and get a strong hold on the human body, and it tips the balance to where the body cannot overcome it and shut it down.

Additionally, the stress typically continues for some time and so your immune system cannot recover until the stress resolves, so it remains compromised. Meanwhile, the pathogen is in control of things, and the body desperately tries to gain control but fighting a losing battle as the pathogen gets an ever stronger gain on control. Comments on this line of thinking?

6. Enter methylene blue. Remember MB has been used OTC for fish tanks, to cure something called "ick" which can kill fish if not treated. I think ick is a fungus, but am not sure. Most white ratters using MB that I have read about get it from aquarium shops, don't know if that is a good idea, though. MB has also been used for years on people (including US military for malaria, I believe it was). It can turn your urine blue, and if you take a lot, apparently can turn the whites of your eyes blue. Freaky, yes. But what if it can help with PD as well?

We now have studies showing neuroprotection/improvement in both Alz. and PD: the TauRx study that diego24 posted (on humans, very impressive) and the MB study Rick posted (equally impressive study done on rats, coming soon to a human white rat near you for comfirmation by trial of one ). An internet search shows that MB has been studied for neurological implications for several years, so while these studies are relatively new, the idea that MB may be beneficial is not. There is something there.

Does MB help because it gives up an electron as we've discussed? Or because it is eliminating some pathogen we dont' know we have? Or both? In the study Rick posted, MB more than doubled the oxygen consumption rate-that is huge. If you go to the full article of that study, you can get exact results and they are significant. If that could be replicated in humans, well, that is also huge. Our neurons could well be suffocating, due to lack of sufficient oxygen, caused by, perhaps, some pathogen. Or MB gives up an electron and bypasses a defect in the mitochondrial process. Either way, MB helps PD.

7. Now, I have recently learned that the nasal mucosa is the ONLY place in the body where nerves go directly from the brain to outside of the body. What if someone has a pathogen on their hand/finger, and they rub or pick their nose? The pathogen gets in, and has a direct route to the brain.

8. This could also help explain why PD is found in some families. A family could have an inherently weaker immune system, which renders the host/family members more susceptible to invasion by a pathogen. Someone in the family has PD....and therefore, under this theory, a pathogen...the pathogen gets spread to another family member who just happens to have the same or similar inherently weaker immune system...and there you are. I'm not saying this explains everything, because there are millions of people who have PD but their spouse does not. But maybe that is because the non-PD spouse has a naturally stronger immune system and it simply is not as susceptible to the pathogen.

One problem with the pathogen theory is that it may defy detection: if we dont' even know a pathogen exists, we cannot possibly test for it. Compound that with the possibility that PD may be caused by different pathogens, some or all of which we have no idea exist, and testing, and treatment/cure, becomes even more difficult to develop. When you don't know what you are looking for, there really cannot be a meaningful search.

I have written this rather hastily this morning so forgive any grammar/punctuation, etc., errors!

Thoughts?

To be honest, I don't believe some virus or bacteria is causing PD. I do believe a viral or bacterial infection could trigger PD, but I don't think a virus is causing the whole PD process. But of course, I can't prove this. This is up to the scientists to prove it.

But if a virus or bacteria would be the cause for PD, then why majority of PD patients have late onset PD ? And those with early onset PD have some genes that gives them a high probability of getting PD ? If a virus or bacteria would cause PD, then anyone could get it no matter what age (and even genes) they have. Also, when scientists converted skin cells into neurons, these neurons also had PD; but no bacteria or virus is causing it.

I tend to believe the common story a bit more; the story that some external events can trigger PD. And a bacterial or viral infection can be such an external effect that triggers PD. I heard that doctors have a much higher probability of getting PD than the normal population. Don't know whether that is true.

Anyway, the question you are asking is really a tricky one and I don't think anyone can answer it. Not even scientists know were PD comes from.

All IMHO:

PD is seen primarily late in life because the immune system gets less efficient as we age. Those with stronger immune systems will get it, if at all, much later. I know of seniors close to 100 who never had PD and were rarely, if ever, sick. I'm sure there are lots of examples the other way, too, though.

I think we could look at the overall health of someone pre-PD perhaps, did they get sick very often, ear infections, colds, flus, general malaise? The problem here is, what is "pre-PD"? The predominant theory is that one has PD for years, sometimes decades, before the cardinal symptoms develop.

We are early onset and got tested at great expense (before 23me) and do NOT have the PD genes (at least, not the "PD genes" that were the main ones at that time, but it wasn't very long ago at all). Go figure.

Neurons made from skin cells of a PWP have PD because the PWP had PD and those cells came from him/her. This may be a stretch, for sure, but if correct it would mean that the pathogen is body-wide.

Perhaps as you suggest a pathogen triggers PD and then the brain imbalance triggers all of the cardinal symptoms. But to me, if that is the case, I see that as meaning a pathogen effectively causes PD. Get rid of the pathogen, there is no brain imbalance, and thus no resulting cardinal symptoms...

Thanks for your thoughts.

Lurkingforacure,

My father was recently diagnosed with PD. My father has never been really sick. His immune system has always been very good. Much better than mine. Me, I always had problem getting sick a lot. As a kid, I was always sick. When I did my PhD my colleagues even told me I was always sick. But my father hardly got sick. Even more ... my father was in perfect state until he got problems with his prostate. This is something that men of his age typically get. The doctor prescribed him some alpha blocker to relax his prostate. He started taking it a year and a half ago. We all noticed that since he took this pills, he started to move slower and his posture was changing. But we didn't link this to PD. We hardly knew what was PD.

For us, his PD started when he took this alpha blockers for his prostate. This was the moment we saw him change. He constantly fell asleep behind his computer. Before these pills, he didn't fall asleep that much. The doctor says the pills are not known for causing PD. But to me that is ********. I know what I saw. Before them, my father was perfect. He was fast and had normal posture. Once taking them, we saw him change. After some research on the internet we found out these pills have an effect on the sympatic nervous system. ... Last week I found out that MJFF foundation is investigating whether PD is the consequence of something that happens to the sympatic nervous system ... Coincidence ? I think not.

I am not saying there are no other ways to get PD. I am convinced bacterias and viruses can trigger PD. To me, this is way doctors have an increased risk of getting PD. But I don't think this is the only way to get PD. There are also links with toxic metals and pesticides. Probably there are even other links that we yet have no idea about. Mohamed Ali got it from getting punched over and over again. I even read articles that claim a wiplash can cause you to get PD.

It is an interesting question to answer ... but at the same time, not an easy one.

Thank you for initiating this discussion.

It would, indeed, require far more time and energy than I have available to do this justice, but I will make a pass at it. Please indulge me to this extent- Unless noted as "IMHO", I can cite a peer reviewed source for any of this but it would take forever. If a critical point needs it I will try to find it here on the "Hard Disk from Hell" but I ask your indulgence otherwise.

Start in the middle. Causes come from one side by multiple paths. Effects leave in the other direction and quickly branch out to our individual manifestations. In the middle is a system-wide collapse of our ability to maintain balance (homeostasis). Insert "IMHO" there somewhere

So we need to picture an hourglass shape. At the "waist" of the hourglass lies a slow motion wrestling match between your immune system and your endocrine system. At ringside sit your GI system and central nervous system (CNS). They take some damage and add to the confusion, but the main event occurs as your increasingly exhausted endocrine system seeks to control your overly alert immune system.

The struggle can begin at middle age as a result of normal increase in the "touchiness" of the immune cells. This is senior onset. It can begin in your twenties with a challenge such as the flu followed by an incomplete shutdown. It can begin in the womb when your emerging immune system is influenced by maternal immune responses. It can even begin two or three generations back with events which altered your mother's endocrine system and which are reflected in your own make up.
(to be continued - I have a ride coming)

[
"When proteins go bad, they often cause disease, but they always have a normal function in our cells," Guy Caldwell said. "We looked to find molecules -- not necessarily that reversed the mutated form of the protein -- but instead enhanced the normal activity of the protein, thereby overcoming the deficiency caused by the mutant."

The UA researchers discovered that ampicillin, a common antibiotic of the penicillin group, serves to activate torsinA, which, in its normal form, appears to protect cells from stresses, such as protein misfolding -- a problem known to impact various movement disorders.

Using a nematode animal model designed to evaluate torsinA activity, the UA lab rapidly screened through hundreds of compounds to identify those that were most effective at enhancing torsinA's normally protective function.

"From there, we collaborated with researchers at Harvard and UAB to validate our findings in human patient cells and mice," said Dr. Kim Caldwell, associate professor of biological sciences at UA.

"In human dystonia patient cells, ampicillin was efficacious and restored the patient cells back to the normal function," Kim Caldwell said. "And, the drug restored normal movement to mice that were genetic mimics of dystonia."

Collaborators in the UA-led study were Drs. Xandra O. Breakefield and her colleagues at Harvard and Yuqing Li and his colleagues at The University of Alabama at Birmingham, known as UAB. Dr. Songsong Cao, a former doctoral student in the Caldwell Lab, is the study's lead author; two UA doctoral students, Alexander J. Burdette and Pan Chen; and one former UA student, Amber Clark Buckley, are among the co-authors.

Furthermore, the research shows ampicillin enhances the capacity of torsinA to protect, within animal models, the neurons which produce dopamine from dying. The death of these neurons in human brains leads to the hallmark symptoms of Parkinson's disease.

As someone whose symptoms of parkinsons were greatly diminished by 10 days of 750mlg of Amoxicillin,(as i reported on this site) I think that
TorsinA is a more logoical theory for its effect than killing a pathogen. Unfortunately powerful antibiotics cannot be taken on a regular basis,and i don't think mild ones like Minocycline are as effective. Nevertheless i have been experimenting with herbal antibiotics like olive leaf extract with some mild success.
On a side note Diego, i was recently put on an alpha blocker Terazosin and immediately noticed a worsening of my parkinsons symptoms. It also made me very tired. I'm now on a beta blocker and feel much better

The issue, as I see it, is whether pathogens continue to play a role once the disease is triggered.

(Note: I use "pathogen" to mean both biological and non-biological agents. I include environmental effects.)

Can epidemiology give an answer?

Suppose you have two identical people whose PD starts at the same time. One goes to live in a high pathogen environment and the other in a low pathogen environment. Then, if the role of the pathogen is solely to trigger the disease, we would expect them to progress at the same rate. Alternatively, if pathogens continue to play a role, we would expect the disease of the person living in the high pathogen environment to progress faster.

We can't get this data experimentally, but we should be able to sift the answer from epidemiological data.

I assume in what follows that the data has been normalized for age, gender, race, socio-economics etc, and that the granularity is such that genetic cluster effects are smoothed out.

We start by noting that if pathogens play a part in the aetiology of PD, the incidence rates of neighbouring areas will be correlated. However, this correlation would not differentiate between the role of pathogens in causing the disease to trigger and their role in the progression.

To separate out these two effects, we focus on disease duration; for PD the time from diagnosis to death. For something that is incurable, disease duration is given by prevalence divided by incidence.

Next, we could again reason that if pathogens continue to play a part, duration statistics for neigbouring areas will be correlated.

Does anyone know of research in this area?

My hope is that soon the Parkinson's community will be organised enough to get a preliminary answer to such questions in one day. YES, ONE DAY!

John

Speaking of pathogen's, does anyone with PD have or have been treated for H. pylori caused ulcers?

Our mouse model demonstrates a direct effect of H. pylori infection on development of Parkinson’s disease. Age dependence, locomotor defects, and neurodegeneration all parallel disease parameters seen in humans. The observation that not all H. pylori strains are equally able to cause Parkinson’s disease will allow us to investigate bacterial factors and/or immune response to H. pylori infection that increase the risk for Parkinson’s disease. Our ability to induce disease using H. pylori extracts will allow us to investigate how modified cholesterol or other substances are taken up in the GI tract and transmitted to the brain.

http://gm.asm.org/index.php?option=c...id=46:newsroom

This is not a new article, 2006, but it fits into the pathogen theory:

http://www.bmj.sk/2006/107067-01.pdf

personally, i think brain cells can die from many causes, including from pathogens. i also think if pathogens were the primary reason for pd it would occur much earlier and in infants who haven't developed a strong immune system.
plus there would be obvious clusters.

antibiotics are fed to chickens since by doing so they pt on weight faster, antibiotics have affects on normal cells, not just bacteria. it is very difficult to get a new antibiotic approved due to side affects and the most powerful antibiotics have strong side affects, often neuropathy.

is pd more prevalent in immune system diseases such as aids? cancer is. that's a highly studied population.

do they have a higher incidence of pd in the humid south east or on the olympic peninsula of wash state cuz fungi sure live year round there and in greater diversity? how about in indonesia or other tropical areas? a higher incidence would stick out like a sore thumb.

i think we get pd mainly after middle age mainly because of following possibilities:
1. repair mechanism breaks down with age after which toxins have more affect
2. gradual buildup of alpha-s
3. maybe just born with fewer dopamine producing cells
4. like with mohammad ali, blows to the head killed cells and eventually the normal 1-2% loss of dopamine cells resulted in pd. we have such a large surplus.

i don't accept the premise that 50year olds have a weakened immune system such that a bacteria can suddenly take hold. my impression is that pd starts years before it is diagnosed, possibly in the 30's, but we have so many extra neurons it doesn't manifest itself until 50's.