Ok....but here's right about the point where the connection with MHC (and chromosome 6) would need to be made. This part is crucial to integrating your theory with MS. If that is missing in any way, I'll bet you a million dollars that nobody in MS research will even listen to you. They have
isolated that MHC, which involves self-recognition (and its associated chromosomes and genetic haplotypes) is definitely involved in MS. They have gotten that far for certain. (I'll paste below a layman's description of MHC). So, I was basically correct before when I said you would need to show a direct connection at some point between your hypothesis and MHC, especially MHC II. (I only just now confirmed it to myself, is all. HAH!)
If there is fragmentation or epigenesis such as you suggest going on, it's at that point. Involving chromosome 6. (Dr. David Hafler is the best in the field as far as that goes. Refer to his findings. I think his findings and yours are real close to meshing. There's just a small "gap", shall we say, in your thinking and his. But you may be able to bridge that gap somehow.) I can sort of "see" it, but I can't verbalize it. That doesn't mean I'm convinced that it's a CORRECT hypothesis or anything, because as you said, it would require a lot more than just hypothesis. And proving it, though, might be something else altogether, but I can't even begin to talk intelligently about that part.
Another thing I've realized is that (in layman's terms), there are sort of different definitions of the word "autoimmune". During my discussions with Dr. Sam Hunter, he used to like to play word games with me. He'd say only one word, and then say "you're a smart woman.....figure it out". Going back to my and Sam's "discussions" regarding whether or not MS was actually an "autoimmune" disease, he'd simply say DEFINITIVELY "Yes, it is." I'd say "maybe not". He'd grin and say "Oh, yes it is". And then he'd tell me to figure it out. LOL
Ok......In talking with you Wesley, and doing further research, now I see what he was telling me. Sam was using the word "autoimmune" to mean "self recognition process". Ok........the self-recognition physiological process, i.e. the BIG picture of it, also includes all of those processes that occur WAY before the "immune system", as we think of it, gets triggered. Which MHC involves self-recognition. (That bugger! THAT'S what he was wanting me to figure out!
Sam found that out himself YEARS ago. He did a lot of the initial research on MHC! Good thing I used his own research when I did mine! He asked me where I got some of it, and I told him that a lot of it was his own! He grinned about that one.) BUT.....like I mentioned previously, that starts getting into "gene therapy", even if it is therapy directed at polyamines, ptx3, p53....any of those. You are still basically talking "gene therapy"; even to prevent what you are talking about might be happening, Wesley. That's where it gets tricky!
So....in the meantime, the best focus that they can do at the moment is trying to stop the cascade of events that happens later on in the process. They are simply attempting to interrupt the process at a later time in the "domino effect", as I call it, when there is less risk to the patient. You can either correct or interrupt the process earlier on (such as what you are suggesting would probably need to be done), or at any point subsequent. Just like dominoes. You can interrupt the downfall of dominoes at any point (before the end) IF you can interrupt one of the dominoes anywhere in the line.
No WONDER Sam was interested in my research on desipramine! I hit something even better than I realized. I did what I am suggesting to you, Wesley. I found the connection of desipramine being a mild "gene therapy" that helps to prevent the changes in DNA fragmentation and its beneficial effects on MHC. (hmmmmmmmmm.....I wonder what Sam will do with my research now. LOL) I understand now, also, why he was shocked at what I had found, why he said "But we can't prove it". We didn't have a LAB! Not one the size you would need in order to do the appropriate research on it! And I won't go into how you can't just walk into a University and say "Hey, can I borrow your lab?" AHA!
Well, Wesley, I'm definitely interested in hearing more. This is getting good. And I think I'm more correct than ever. Dr. Sam Hunter would be your "guy" if you can get to him. I did send him an email and told him about you, by the way (but of course, I couldn't say much about you....how much do I know?), and that you MIGHT look him up when he's in Tampa next week. I can't guarantee
that he'll listen to you, or even give anybody the time of day, but he's your best bet. He's about the only one who's open enough to consider new ideas. If he seriously considered mine (and still does), then he might be open to considering yours. The problem is, also, that he's spread so thin right now. That's why I said, also, that not only would your theory need to be strong, but Sam has a PhD in pharmacology/toxicology and is an immunotherapist and he's concentrating right now on MS treatment, so an additional avenue to capture his interest would be to provide some valid speculation on what current or new type of therapy might apply, also. (Maybe desipramine! HAH!) I still think that at least on paper, desipramine is almost taylor-made for MS. Sam did, too.
In any event, I look forward to hearing more from you when you have time.
The major histocompatibility complex
30/7/03. By RT
A cluster of genes essential to the immune system.
The major histocompatibility complex (MHC) is a large cluster of genes found on the short arm of chromosome 6. The complex spans four million base pairs of DNA and contains 128 genes as well as 96 pseudogenes (non-functional gene remnants). Many, but by no means all of the genes in this complex play important roles in the immune system.
Traditionally, the MHC is divided into the class I, II and III regions, each containing groups of genes with related functions.
The class I and II MHC genes encode human leukocyte antigens (HLAs), proteins that are displayed on the cell surface and define an individual’s tissue type (see article on tissue matching). There are many possible tissue types in the population because each HLA exists as a large number of varieties. Everyone’s immune system is tolerant of its own HLAs, but if foreign HLAs are detected then the cells displaying them are attacked and destroyed. This is why the body rejects grafts and transplants from donors that have not been matched for tissue type.
The class I and II MHC proteins also perform the important function of antigen presentation. This is how the immune system finds out what is happening inside our cells even though it can only survey them from the outside. Proteins inside the cell are broken into short fragments and displayed as peptide antigens by MHC proteins on the surface. This helps the immune system to discriminate between normal (self) antigens and those that are foreign and potentially dangerous.
Class I MHC proteins are found on virtually all cell types and their job is to present fragments of proteins that are synthesized inside the cell. The peptide antigens presented in this manner are checked by killer T-cells, which have receptors for the class I MHC proteins. The purpose of this surveillance system is to identify abnormal body cells, such as those infected with viruses or those that have turned malignant. Such cells will display unfamiliar peptide antigens, e.g. fragments of viral proteins, and are attacked and destroyed.
Class II MHC proteins are found only on immune cells such as phagocytes that engulf foreign particles such as bacteria. These cells are specially designed to present peptide antigens derived from such digested particles. The antigens are presented to helper T-cells, which have receptors for class II MHC proteins. The purpose of this surveillance system is to stop the immune system running out of control and attacking the body’s own cells. Only if the presented antigen is recognized as foreign by the helper T-cell is the phagocyte allowed to survive.
Class III MHC genes encode several components of the complement system, a collection of soluble proteins found in the blood that targets foreign cells and breaks open their membranes. Adjacent to the class III region is a group of genes that control inflammation. Further genes with various immune and non-immune functions are dotted throughout the complex.
The MHC shows a high degree of polymorphism (100 times higher than the genome average, i.e. a 10 per cent difference between any two unrelated individuals). Many of these polymorphisms appear to be associated with either increased or decreased susceptibility to a range of infectious diseases including malaria, tuberculosis, leprosy, typhoid fever, hepatitis and HIV/AIDS.
Defects in certain MHC genes lead to autoimmune disorders in which the body fails to recognize self-antigens. Examples of such diseases include multiple sclerosis, some forms of arthritis and diabetes, and inflammatory bowel disease.