Multiple Sclerosis results from having anti-myelin B and T lymphocytes in your cerebrospinal fluidIn other words, having antibodies (secreted by B lymphocytes) and T-lymphocytes (which have special binding sites, unwisely named "T Cell Receptors" on their outer surfaces). These binding sites exactly fit a certain protein made only by the oligodendrocytes, which are the central nervous systems's equivalent of Schwann cells. (Schwann cell myelin doesn't get attacked: Not in people with MS, nor in any autoimmune disease. To repeat, there is no equivalent to MS in which Schwann cell myelin gets attacked by the immune system. We should be curious why not.
What Goes Wrong in Multiple Sclerosis?
Possibility A) Maybe the "weeding out" mechanism fails to kill or inactivate (or whatever it does) a few B and T lymphocytes whose binding sites fit that certain protein found only in the myelin of the central nervous system.
Possibility B) Perhaps the CNS myelin protein (sometimes) doesn't get made until after the weeding-out mechanism has finished operating. Myelination has barely begun at the time of birth, I was surprised to read recently.
Possibility C) Perhaps the CNS myelin protein is located at places where no lymphocytes can find it at the time of the weeding-out process.
(Notice that possibilities B and C are special cases of possibility A. They are specific reasons why the weeding-out mechanism could fail to eliminate just those lymphocytes whose binding sites fit this one particular protein.
Possibility D) Maybe the VDJ DNA splicing genes get turned back on, later in life, after the weeding-out mechanism (whatever it is) has stopped functioning. However, that ought to result in anti-self lymphocytes with many different specificities, not just a specificity for CNS myelin. NOTE: Lupus is a major autoimmune disease in which lots of different antibodies are produced: anti-histones, anti-collagen, anti-single-stranded DNA and RNA.
Possibility E) Maybe some peculiarity of the VDJ DNA splicing machinery, when (partially?) reactivated produces lymphocytes which bind just a few certain proteins, especially CNS myelin.
Possibility F) Maybe mutations in genes for Lymphocyte binding sites change their specificity enough that lymphocytes that didn't get weeded out are converted to making binding sites that fit CNS myelin.
Possibility G) Maybe some virus or bacteria produces a protein that happens to have a sufficiently similar shape and charge distribution as the CNS myelin, so that exposure to this germ stimulates lymphocytes...
Please invent more possible causes for production of anti-myelin lymphocytes
What Treatments Are Currently Used For Multiple Sclerosis?
I) Monoclonal antibodies that selectively attack B Lymphocytes. These reduce symptoms at the cost of weakening your immune system, and reducing immunity to germs. Although very cheap to make (using cell lines that secrete particular antibodies), they are sold for thousands of dollars per dose. The drug companies refer to their prices as "costs".
II) Beta Interferon: which is a normal cytokine with many known effects, including inhibiting T-lymphocytes. Take a look at http://www.ncbi.nlm.nih.gov/pubmed/20038758 which contains the following sentence:
Translation: "Nobody knows" And they don't even mention the extremely severe side effects!
III) Random synthetic peptides consisting of tyrosine, alanine, lysine and glutamic acid.
Quotes from the Wikipedia article about "Glatiramer"
" A double-blind 3-year study found no effect of glatiramer acetate on Primary-Progressive Multiple Sclerosis."
Try Googling: " copaxone cost " or " copaxone price"
A Different Method That I Seriously Think Ought To Be Able To Cure Multiple Sclerosis.Make monoclonal antibodies whose binding sites specifically fit the binding sites of the anti-myelin antibodies and T-cell receptors that are what produce the damage in MS. This would mean vaccinating mice with anti-myelin antibody molecules, then getting B lymphocytes from the mice, fusing these with myeloma cells (cancerous B lymphocytes), and then selecting out fused cells that make antibodies against anti-myelin antibodies. Those anti-antibodies would damage and kill just the MS-causing lymphocytes, both B and T lymphocytes. If they killed all those antimyelin lymphocytes, then the disease would be cured; if they just killed some of the antimyelin lymphocytes, then the symptoms would be reduced, without the harmful side effects of the treatments now being used.
BUT, is it practical to make monoclonal antibodies whose binding specificity is for the binding sites of other antibodies? I think that it should be. Here is evidence: Cancer researchers (in the laboratory of R. Levy) have succeeded in stimulating formation of monoclonal antibodies that bind selectively to the antibodies of malignant B lymphocytes. Furthermore, these anti-antibodies produced long and possibly permanent remissions from types of non-Hodgkin's lymphoma that are otherwise fatal.
Unfortunately, to treat cancer this way requires preparation of a new and different monoclonal antibody for each individual lymphoma patient. That would cost many thousands of dollars, perhaps even tens of thousands of dollars per lymphoma patient. This is "not economically feasible" in the words of the best immunology textbook (Kuby's Immunology).
In comparison, lymphoma patients are routinely charged hundreds of thousands of dollars for treatment with monoclonal antibodies specific for all B Lymphocytes. Those monoclonal antibodies cost only a few hundred dollars to make enough for an average human dose. In other words, the drug companies require hundred-fold profit margins, or they won't bother to develop a treatment based on a method that has been proven to cure people.
Fortunately, in order to treat MS with monoclonal antibodies, you would not need a different clone of antibody-secreting B lymphocytes for each patient. The same antibodies that would bind to one person's anti-myelin binding site would work just as well for any MS patient. Please tell me what you think about this way of treating MS. What can I do with such an idea?
Market economies work by incentivizing corporations to optimize profits. This is usually a good system. But it can have harmful effects in special cases. In particular, a drug that actually cures a disease, and that patients don't need to keep taking, is much less profitable than a drug you must continue to buy and administer. A cure for MS would bankrupt the same corporations that get to decide which methods of treatment will be tried, versus which ones are "not economically feasible".
The drug companies realize this, and if you think they are self-sacrificing enough to risk bankruptcy, just in order to save a few thousand lives, good luck. They think of themselves as already doing lots of good, prolonging lives. So it seems to them unreasonable that anyone should expect them to reduce their profits ten-fold, or worse. They never discuss this issue, even in private, in sentences like "Watch out, that treatment would work too effectively, and reduce profits!" But such things need not be said out loud. On the other hand, speeches do get made about the virtue of converting MS and cancer into chronic diseases, that only shorten lives by a decade or so.
That behavior is being incentivized. Average people are too nice to imagine that anybody would hold back the discovery of cures, for financial gain. But lots of people would do exactly that.
The following is a sample paragraph from this very interesting and intelligent site:
"One last factor driving costs [by which he means doubling the price] is that the patent on Copaxone is expiring in 2013, and three other companies are lined up to knock it off. It is very cheap to make, 1960s technology, and TEVA pharmaceuticals has been wildly profitable due to the recent increased revenues, low production costs, and captive market, since unlike interferon-beta, no glatiramer products compete in the market. The actions of TEVA can only be described as nonadmirable and most would consider it an abuse. At the same time, they started providing much less assistance. Most of my colleagues have interpreted it as greed, pure and simple, the worst of capitalism. TEVA also embarked on a landmark course of suing other companies to stop them from doing what is legally permitted. Ironically, in the past, TEVA has usually been the one knocking off other drugs and getting sued. Both US Food and Drug Administration and the European counterpart have stated that Copaxone can be simply knocked off as a generic drug. TEVA has unfortunately suffered a major failure in drug development of laquinimod." [another anti-MS drug]
To read about "laquinimod", see http://www.ncbi.nlm.nih.gov/pubmed/26000222> I haven't found out its chemical structure. "...a comprehensive review covering clinical efficacy and safety data obtained from two phase III clinical trials, as well as the presumed beneficial mechanism of action of laquinimod. This article also provides a short overview of the oral DMTs recently approved for the treatment of relapsing MS, as well as challenges that still remain to be overcome to fully control the relentless course of MS."
How could they patent a random co-polymer?