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Autoimmunity theory

Posted: Fri Jun 22, 2007 7:38 am
by dignan
Step 1: find abstract on new autoimmune theory
Step 2: post on ThisIsMS
Step 3: sit back and watch fireworks.



Are multiple sclerosis and amyotrophic lateral sclerosis autoimmune disorders of endogenous vasoactive neuropeptides?

Med Hypotheses. 2007 Jun 18;
Staines DR.
Gold Coast Public Health Unit, 10–12, Young Street, Southport 4215, Queensland, Australia.

Autoimmune dysfunction of endogenous vasoactive neuropeptides (VNs) such as vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) has been postulated as a cause for some fatigue-related conditions. VN receptors are class II G protein-coupled receptors (GPCRs) which couple primarily to the adenylate cyclase (AC)-cyclic AMP (cAMP) pathway and cAMP has a central role in neurological metabolism including influencing blood-brain barrier (BBB) and blood-spinal barrier (BSB) permeability, coordinating neuroregulatory pathways, and protecting against neuronal apoptosis.

Complex clinical signs occur in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While traditionally viewed as diseases of the motor system, the clinical picture of these conditions is considerably more complex. Disturbances of cognition and memory, as well as emotional lability occur along with fatigue and motor dysfunction.

This paper explores the hypothesis that autoimmune dysfunction of VNs may contribute to MS and ALS. While MS and ALS differ in important respects, they have common pathogenic features including inflammation, oxidative stress and mitochondrial dysfunction. Apoptotic mechanisms are associated with activation of caspase pathways and functional interplay between proinflammatory cytokines, interferon gamma and nitric oxide is suggested associated with oxidative stress and glial activation. Diseases such as MS and ALS may represent related conditions resulting from variation in expression of different receptor subtypes of the VN family. Anatomical differences of these receptors, perhaps in areas overly dependent on a specific VN receptor sub-type, may predispose to autoimmune susceptibility to these conditions, either in impaired expression of receptors or antibody and cellular immune targeting of them.

Further studies are required to determine if such VN receptor sub-types of significant specificity exist and if they are susceptible to compromise. This hypothesis, if proven, may have implications for the development of treatment and preventive strategies.

Pubmed URL

NONautoimmune camp

Posted: Fri Jun 22, 2007 6:12 pm
by lyndacarol
Here I am (as you, no doubt, anticipated).

As I have quoted before from The Language of God by Francis S. Collins on page 61:
A variation on Ernest Rutherford's dictum is famously known as Occam's Razor, a misspelled attribution to the fourteenth-century English logician and monk William of Ockham. This principle suggests that the simplest explanation for any given problem is usually best. Today, Occam's Razor appears to have been relegated to the dumpster by the bizarre models of quantum physics.
Because scientific explanations are beyond my abilities, I think on a much simpler level. Could researchers be making this more complicated than necessary?

If MS is the result of an overactive immune system, MS and AIDS (NO working immune system!) should never exist in the same individual--but I have read that there ARE AIDS patients with MS (tho I can't put my hands on the source right now)!

And drugs that modify the immune system should be wildly effective!

Just put me in the camp with those who believe that MS is not an autoimmune disease.

Posted: Fri Jun 22, 2007 10:05 pm
by Lyon
Image
Hi Lynda,
I agree that a good percentage of MS researchers have overcomplicated things to the point that they are only making advances in getting farther from the truth. NOTHING is that complicated and if MS REALLY were that complicated they might as well give up now because the answers are forever going to be beyond their understanding.

On the other hand it's a common misconception that AIDs by definition is only the complete lack of an immune system. Although shortly before death some people with AIDS might reach that point, with current medications the stages of AIDS can be extended indefinitely. Someone with AIDS might realistically be no more immune suppressed than someone on one of the crabs. It doesn't take any stretch of the imagination and it's not contrary at all to consider that AIDS and MS can coexist in the same person.
lyndacarol wrote:And drugs that modify the immune system should be wildly effective!
ANY modification of the immune system should be wildly effective? That's far too vague and inaccurate.
lyndacarol wrote:Just put me in the camp with those who believe that MS is not an autoimmune disease.
Another membership into the few and proud Flat Earth Society eh? Tovaxin removes only the myelin reactive T cells and seems to show good results. Campath 1h and High Dose Cyclophosphamide reputedly eliminate the entire immune system and allows a healthy one to grow back and seems to show good results. We have at least two members of this forum on Campath 1H who haven't experienced progression since. No one can say those results will last forever but even a temporary profound result conclusively proves that autoimmunity is involved in the MS process.

Bob

Clarification of definitions

Posted: Sat Jun 23, 2007 4:13 am
by lyndacarol
Lyon--I love your fireworks animation!!!

You wrote:
even a temporary profound result conclusively proves that autoimmunity is involved in the MS process.
I feel I need to clarify my words: I do believe the immune system is involved in the MS cascade (I happen to think that excess insulin starts the process.). I do not think the disease is autoimmune. As someone at this site once wrote: Would the body wake up one day and attack itself for no reason; then remit; then attack again?

Posted: Sat Jun 23, 2007 4:18 am
by robbie
two members of this forum on Campath 1H who haven't experienced progression
Bob how many people are on Campath,? and does it have 100% sucess rate like Tovaxin, seems like these are the only two things that boast these kind of numbers.
For 14 of these volunteers, the progress of their disease initially appeared to be completely halted. In the remaining 13, however, their MS symptoms continued to worsen even in the absence of new inflammatory lesions. MRI studies have discovered that the trial subjects, whose disease continued to progress, were the ones that had the greatest amount of existing lesions and brain atrophy. Unfortunately, as time goes on, it appears that even some of those people whose progression appeared to have been arrested by the drug are now beginning to deteriorate as well. These results have led Campath's researchers to make several important inferences:

Re: Clarification of definitions

Posted: Sat Jun 23, 2007 8:58 am
by Lyon
lyndacarol wrote:Lyon--I love your fireworks animation!!!
Hi Lynda,
I took robbie's advice and started a photobucket account and downloaded a fireworks.gif file to it. It was originally a prettier color though!
lyndacarol wrote: Would the body wake up one day and attack itself for no reason; then remit; then attack again?
I used to think that was a sensible and obvious argument but several times recently Tim Wesner has stated that everyone produces myelin reactive (read that "attacking") T cells and the difference between those with MS and those without is that the systems of those without MS keep the number of those mrtc's under control. I don't know his source for that information but Tim has inside information with Opexa researchers and those researchers likely are in a position to make that determination.

If that is true, any arguments regarding how MS starts or whether is an autoimmune disease are rendered meaningless and we can only accept that autoimmunity is a natural process in all humans and that the inability to keep that process under control is the problem with people with MS and the other autoimmune diseases.

I'm not in a position to dictate that everyone believe in autoimmunity but the abundance of evidence and increasing evidence shows that MS is entirely autoimmune.

robbie wrote:Bob how many people are on Campath,? and does it have 100% sucess rate like Tovaxin, seems like these are the only two things that boast these kind of numbers.
Hi robbie,
I'm not a real follower of Campath so I don't know those answers but I do know that unlike current MS medications in which it's been an ongoing struggle to determine whether or not they really provide benefit over placebo, Campath provides obvious benefit.

For the sake of my friends on Campath I hope that it proves safe and effective over the long haul but my only interest in this argument is only that it makes a profound and obvious difference in the MS disease process. I admit that Campath isn't perfect and that it will have to eventually be modified or something better developed but for now it offers advantages over current MS medications and it's becoming more accessible to MS'ers. Not a perfect situation but beneficial.

You might find this recent and informative article interesting http://tinyurl.com/2onekn

Bob