How to Cure Multiple Sclerosis

Current methods: (which slow the rate of worsening of paralysis by 25-35%)

No treatment yet discovered stops worsening, let alone curing MS!)

I) Beta Interferon (a normally occurring cytokine protein) which the body produces during viral diseases. The pain, fevers and extreme misery that you feel during influenza are caused by interferons alpha, beta and gamma. When these 3 proteins were first synthesized in bacteria (and could therefore be made very cheaply) they were randomly tried as possible treatments for many incurable diseases, including lymphoma and MS, although there was no biological reason to expect they would have any effect.

Beta interferon, for some unknown reason, slows the rate of worsening of MS symptoms, but at the cost of so much misery that some patients prefer to die than continue the flu-like side effects.

II) Non-specific immune suppression by cortico-steroid hormones. (Which has much less painful side effects). Weakening your whole immune system is itself a serious side effect, because you become much more likely to die from bacterial and viral diseases.

(Like MRSA [Methicillin resistant Staphylococcus aureus] and Clostridium difficile.)
(According to Wikipedia, "C. diff" kills 14,000 Americans per year. )

III) Non-specific immune suppression by cancer chemotherapy drugs, especially cyclophosphamide = "Cytoxan" (nitrogen mustard-gas chemical) These cause breakage of chromosomes, nausea and kill faster-growing cells, and non-specifically damage all parts of the immune system. The slowing of deterioration caused by MS is a non-specific side effect of this immune suppression, and therefore all the effects, like MRSA susceptibility.

IV) Monoclonal antibodies that specifically bind certain cell-matrix adhesion proteins, which was intended to inhibit the locomotion of t-lymphocytes into the brain.
(And really works! But only slows worsening.

V)Some other drugs that I will add to this list later.

VI) "Glatiramer acetate" = Copaxone (Two made-up names meant to sound scientific, and to insinuate that this material is a specific chemical). Really, it is a +/- many-thousand Dalton random sequence of four particular amino acids: Alanine-Glutamic acid-Lysine-Tyrosine. (note for those who remember their molecular structures, why not co-polymerize Valine-Aspartic Acid-Arginine-Phenylalanine, which should have about the same properties. (one hydrophobic, one acidic, one basic, and one with a benzene ring).

You can find patent information about it on the internet. The manufacturers seem not to realize that any such copeptides can be cheaply synthesized by mixing any proteolytic enzyme with very high concentrations of the amino acids you want to polymerize. The high concentrations will cause the proteolysis to run backwards. All enzymes speed up their reactions by the same ratio in both directions.

This past spring and summer, the company that owns the patent on Glatiramer has been vigorous suing in US federal courts to prevent sale of generic versions of this stuff. Their position is that competing companies should be required to test the stuff on as many human volunteers as were used in the original tests. (Over a thousand people.)Think about what would be required to satisfy this demand.

Despite its strangely random chemistry, Glatiramer really does slow down MS by about 30%, and its side effects are much less bad. Its mechanism of action has yet to be discovered, and I couldn't find evidence of research, for example about its binding to anti-myelin T-lymphocytes, or about the relative effectiveness of peptides made out of different combinations of amino acids, or tests of effects of D-amino acids, or lots of other kinds of experiments you can invent, based on having taken organic chemistry .

This stuff was "invented" (if that's the right word for a semi-random peptide that nobody knows how it works) forty years ago. It was injected into rabbits to test whether it would induce auto-immune inflammation of the brain (which can be induced by injecting ground-up brains). Unexpectedly, the copolymer did not induce autoimmunity, but did inhibit or prevent the injected rabbits from developing the usual autoimmunity when these same rabbits were injected with ground up brains. So they patented it and tried it on several thousand human MS patients. Its sales produce 3 and a half billion dollars per year, and the prices (which they call "costs") are more than fifty-thousand dollars per year per patient. You can buy it at Walmarts, etc, for $ 5,349.72 per 30 injections.

And at Walgreens for $6,594.00 (and no cents! Keep the change.

http://www.goodrx.com/copaxone

I would like to find out the approximate total amount of money spent on MS research per year. Probably a lot less than one billion dollars.

Please read the web site of the National Multiple Sclerosis Society

They have lots of important information, part of which is that science is a long way from finding a cure, or even knowing which research directions are most likely to produce a cure. They think in terms of "managing your disease" by means of "disease modifying substances".

Possible cures: (trying to focus on specific properties of molecules and cells that cause MS)

1) Cause regeneration of brain myelin to transcribe genes normally expressed in Schwann Cell myelin, instead of the kind of myelin made inside the central nervous system (because the only latter is what gets attacked in MS).

2) Chemotactic attraction specifically of anti-myelin lymphocytes, causing them to go somewhere that they die or are less harmful.

3) Anti T-cell T-Cells. Stimulate and isolate clones of either b-lymphocytes or t-lymphocytes whose binding sites have exactly the shape and charge distribution needed to bind to the binding site of the anti-myelin lymphocytes. (Note: Many monoclonal antibodies have been made that selectively bound to the binding sites of lymphoma b-lymphocytes, and these selectively killed just the patients' cancerous lymphocytes.

It would be cheaper to create a clone of anti-anti-CNS myelin T-cell receptors.

4) Modern "chip" technology is based on using robot-controlled micropipettes to synthesize thousands of alternative nucleic acid base sequences. Imagine adapting the same machinery to make many known alternative chains of amino acids, for the purpose of determining what variants of Glatiramer are most effective. Binding of t-lymphocytes from cerebro-spinal fluid of MS patients seems to me to be a practical criterion.

5) The destruction of oligodendrocytes is probably by apoptosis, which can be prevented by over-production of the bcl-2 protein (genes for mimics of which are encodedin many viruses. Researchers are now trying to replace MS-damaged myelin using injections of stem cells into the brain. It seems more practical to protect the oligodendrocytes from destruction than to than to replace them with stem cells (among other reasons, the new myelin sheaths would themselves get attacked.

6) Reactivate the normal (but unknown) "tolerance mechanism", so that it weeds out all lymphocytes whose binding sites fit anti-CNS myelin proteins.

 

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