Myasthenia Gravis Support Group
Myasthenia gravis (MG) is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest. Although myasthenia gravis may affect any voluntary muscle, muscles that control eye and eyelid movement, facial expression, and...
since I am taking Cellcept, and believing it is working. I asked my Neurologist awhile back "How does cellcept/how can it work for MG? She couldn't give me an answer, and I would imagine many neuros that are not "Experts" in the field may answer the same. She is simply following the teachings of the MG expert from which she trained, not even knowing why she is recommending Cellcept without question. I think it is good that she has seen the results first hand over the years, but nonetheless, I have been taking it upon myself to help her learn what I learn, as she simply doesn't have the time, or will not take the time. Afterall, she does have plenty of other neurological patients that do not have MG, which is to say the majority of her patients do not have MG. She does respond to my emails and thanks me for information also, and I feel we do have a good relationship... Anyway, here is what I found interesting recently:
"Mycophenolate is derived from the fungus Penicillium stoloniferum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes."
http://en.wikipedia.org/wiki/Mycophenolic_acid
So Cellcept is derived from Penicillium fungus, which produces penicillin. So, we got that, and so I was looking at how penicillin helps MG and found:
"These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy."
http://www.amjmed.com/article/0002-9343%2877%2990153-X/abstract
So this would also explain why some people cannot be on cellcept as well, thymic hyperplasia would not be good for young people with MG But, if you are fully grown, it may not matter, but might bother someone that had a thymectomy?:
Thymus Hyperplasia:
"It is not always a disease state. The size of the thymus usually peaks during adolescence, and atrophies in the following decades. Before the immune function of the thymus was well understood, the enlargement was sometimes seen as a cause for alarm, and justification for surgical reduction. This approach is much less common today."
http://en.wikipedia.org/wiki/Thymus_hyperplasia
Also the reason why many people should probably not have a thymectomy if fully grown from adolescence(older folks over 30?), unless there is a thymoma present, of course?
Back to penicillin, as I mentioned, we also saw that "antiacetylcholine receptor antibody", so it attacks them, which could be called bacterias, I guess since penicillin is an antibiotic. That is why it should work. But for people that are sero-negative, MUSK or refractory, maybe not so much...
Why cellcept over Imuran?
"Mycophenolate is potent and can be used in place of the older anti-proliferative azathioprine."
"mycophenolate is increasingly utilized as a steroid sparing treatment in immune-mediated disorders"
" In long-term immunosuppression, it may be used to avoid calcineurin inhibitors or steroids." Whew! That is good news..Right?
http://en.wikipedia.org/wiki/Mycophenolic_acid
Why does Imuran work for MG(both it and cellcept are purine synthesis inhibitors)?
"Azathioprine is a pro-drug. Following oral ingestion, it is metabolized into the active 6-mercaptopurine, itself a purine synthesis inhibitor. 6-Mercaptopurine impedes DNA synthesis and thus inhibits the proliferation of cells, especially the fast-growing lymphocytes. T-cells and B-cells are particularly affected by the inhibition of purine synthesis. Azathioprine is an effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants..."
http://en.wikipedia.org/wiki/Azathioprine (There is info on cyclosporine here too, but i would prefer cellcept or imuran over it me thinks, and overall cellcept due to less to almost none reported overall major side effects, especially long term)
Also for reference:
http://en.wikipedia.org/wiki/Ciclosporin
Mechanisms involved?:
http://en.wikipedia.org/wiki/Hypersensitivity
http://en.wikipedia.org/wiki/Cytotoxic_T_cell
http://en.wikipedia.org/wiki/Antibody-dependent_cell-mediated_cytotoxicity
A lot to take in, but sometimes I get going on a tangent and cannot stop. Here is looking through my eyes, when you have time.
Of course there is polenty of documentation about prednisone and other drugs working as well, so if that is your course of treatment, I wish you well also, and until we find some kind of "cure" for this condition, we mess around with our "mixed bag" of treatments to find that special regimen to make us all feel better.
Here is to feeling better.
Best wishes for peace to all,
TJ
"Mycophenolate is derived from the fungus Penicillium stoloniferum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It inhibits inosine monophosphate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes."
http://en.wikipedia.org/wiki/Mycophenolic_acid
So Cellcept is derived from Penicillium fungus, which produces penicillin. So, we got that, and so I was looking at how penicillin helps MG and found:
"These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy."
http://www.amjmed.com/article/0002-9343%2877%2990153-X/abstract
So this would also explain why some people cannot be on cellcept as well, thymic hyperplasia would not be good for young people with MG But, if you are fully grown, it may not matter, but might bother someone that had a thymectomy?:
Thymus Hyperplasia:
"It is not always a disease state. The size of the thymus usually peaks during adolescence, and atrophies in the following decades. Before the immune function of the thymus was well understood, the enlargement was sometimes seen as a cause for alarm, and justification for surgical reduction. This approach is much less common today."
http://en.wikipedia.org/wiki/Thymus_hyperplasia
Also the reason why many people should probably not have a thymectomy if fully grown from adolescence(older folks over 30?), unless there is a thymoma present, of course?
Back to penicillin, as I mentioned, we also saw that "antiacetylcholine receptor antibody", so it attacks them, which could be called bacterias, I guess since penicillin is an antibiotic. That is why it should work. But for people that are sero-negative, MUSK or refractory, maybe not so much...
Why cellcept over Imuran?
"Mycophenolate is potent and can be used in place of the older anti-proliferative azathioprine."
"mycophenolate is increasingly utilized as a steroid sparing treatment in immune-mediated disorders"
" In long-term immunosuppression, it may be used to avoid calcineurin inhibitors or steroids." Whew! That is good news..Right?
http://en.wikipedia.org/wiki/Mycophenolic_acid
Why does Imuran work for MG(both it and cellcept are purine synthesis inhibitors)?
"Azathioprine is a pro-drug. Following oral ingestion, it is metabolized into the active 6-mercaptopurine, itself a purine synthesis inhibitor. 6-Mercaptopurine impedes DNA synthesis and thus inhibits the proliferation of cells, especially the fast-growing lymphocytes. T-cells and B-cells are particularly affected by the inhibition of purine synthesis. Azathioprine is an effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants..."
http://en.wikipedia.org/wiki/Azathioprine (There is info on cyclosporine here too, but i would prefer cellcept or imuran over it me thinks, and overall cellcept due to less to almost none reported overall major side effects, especially long term)
Also for reference:
http://en.wikipedia.org/wiki/Ciclosporin
Mechanisms involved?:
http://en.wikipedia.org/wiki/Hypersensitivity
http://en.wikipedia.org/wiki/Cytotoxic_T_cell
http://en.wikipedia.org/wiki/Antibody-dependent_cell-mediated_cytotoxicity
A lot to take in, but sometimes I get going on a tangent and cannot stop. Here is looking through my eyes, when you have time.
Of course there is polenty of documentation about prednisone and other drugs working as well, so if that is your course of treatment, I wish you well also, and until we find some kind of "cure" for this condition, we mess around with our "mixed bag" of treatments to find that special regimen to make us all feel better.
Here is to feeling better.
Best wishes for peace to all,
TJ
I think your post may lead people to think that penicillin and penicillamine are good for myasthenia. Actually penicillamine is so bad for MG that it has precipitated crises.
Penicillin works by interferring with cell walls. Since we have cell membranes and bacteria have cell walls, it is safe to take penicillin as long as you are not allergic OR have myasthenia.
As you state, Penicillamine is associated with antistriational antibody [antibody against striated muscle], antiacetylcholine receptor antibody [antibodies against acetylcholine, and we need all the acetylcholine we can get], and thymic hyperplasia [leads to larger thymus, not good].
So Cellcept interfers with the B and T cells made in the thymus that may be making antibodies to our muscles.
Penicillin and penicillamine make everything worse probably by encouraging our B and T cells to produce more antibodies against muscle and the messenger between the nerve and the muscle. (I don't know how this works on a cellular basis.)
*********In short, for us, Cellcept good,. Penicillamine especially bad news.***********
I don't know how the antibiotics make myasthenia worse. I was told that so many medications are trouble because the nerve muscle connection is an open one. But that doesn't tell us what these drugs are actually up to in the junction--in our case, no good.
b.
I am looking forward to hearing from many on this subject to perhaps straighten me out, or at least give me a better understanding, because I agree with what you are saying about penicillin causing problems for people with MG, as one of the links describing how penicillin can help in my post describes it helping and hurting, which is confusing, and led me to describe how cellcept and/or imuran can be beneficial for MG.
"So Cellcept interfers with the B and T cells made in the thymus that may be making antibodies to our muscles."
I read and get more confused:
"MMF is the 2-morpholino-ethyl ester of mycophenolic acid (MPA), a fermentation product of Penicillium stoloniferum. MPA, the pharmacologically active compound of MMF, has immunosuppressive properties due to its ability to selectively, noncompetitively, and reversibly block the nicotanimide binding site on inosine monophosphate dehydrogenase (IMPDH), an enzyme needed for purine synthesis.
This effect manifests clinically as an anti-proliferative effect on T- and B-lymphocytes, inhibition of polyclonally activated B-lymphocyte antibody formation, decreased production of the inducible form of nitric oxide (NO) (reducing tissue damage by nitrites), and the prevention of glycosylation and expression of certain adhesion molecules on lymphocytes leading to decreased lymphocytic and monocytic recruitment and penetration into sites of inflammation.13 It has also been shown to inhibit the superantigen-induced production of interleukins (IL)-16 and 10, tumor necrosis factor (TNF)-a, TNF-, and granulocyte monocyte colony stimulating factor (GM-CSF) using in-vitro-activated human mononuclear cells.4
MMF was initially approved for the prophylaxis of organ rejection in adult renal, cardiac, and hepatic allograft recipients in the mid-to-late 1990s. Soon after, reports of successful treatments of such neurological diseases as myasthenia gravis (MG)..."
http://www.touchneurology.com/articles/mycophenolate-mofetil-immune-mediated-neurological-diseases-comprehensive-review
I am just having a hard time understanding how cellcept being derived from penicillin(er the fungus that excretes it), can be helpful for MG. I took my best guess as to why this is, but...(Imuran either for that matter, but I didn't find any official info on what imuran was derived from despite it serving the same function as cellcept)
Anyone?
Best wishes,
TJ
The cells of fungi and bacteria make many chemicals to keep themselves alive. Some of those chemicals help with internal operation and some are to keep other organisms from destroying them.
Penicillin was discovered because a mold landed on a plate of bacteria and the bacteria around the mold were killed. Fleming alertly grasped the possibilities and medicines from molds began. Then chemists learned what exactly the "active ingredient" was and began to make it in the laboratory. Then they began to make other chemicals with similar structure and tested to see whether they also worked in similar ways. So we have penicillin, ampicillin, etc.
So an organism makes many different kinds of chemicals. They are their own laboratory and their work is not static either--that's why we have drug resistant organisms.
Cellcept is one of many chemicals made by the fungus, and it has a different structure than penicillin, it works in a different way and unless there is contamination or great structural similarity, I wouldn't think people allergic to the one chemical would be allergic to the other.
So evidently our B and T cells that make antibodies in us are especially sensitive to having their purine metabolism interrupted. If all our cells worked in the same way, we couldn't take the drug. Cellcept is a chemical that interferes in purine metabolism.
Whatever it is that penicillin and penicillamine do, it stimulates the B and T cells to reproduce more rapidly and that's where our problem is. I guess we know what some of our B and T antibodies are after, but not why they consider acetylecholine the enemy.
b.
I don't know why scientists have to use such big words and convoluted sentences. Maybe they get paid by the page! Immunology is complicated, but simply stated, it can be simply understood. Scientists do not know everything about the complications so they could just say "I don't know."
b.
What we do with the immunosuppressive drugs is something like trying to get rid of a protruding screw with a sledge hammer. There's a lot of collateral damage. Research is looking for the screwdriver and not just any screwdriver will work.
b.