Sunday, May 11, 2008

Summary of Current Autoimmune Treatments

I wrote the following for a friend who has MS and had to stop IL-1 shots due to side effects. Others may find it interesting as well. In my original word format it was in outline form. I seem to have no luck in putting it in that form with this format. Sorry.

Two Current ways to reverse autoimmune disease including relapsing remitting MS or any other autoimmune disease B cell Depletion Therapy and Bone Marrow Transplant
(1) B Cell depletion therapy has two choices

(a) Rituxan (Rituxamab) which is a chimeric monoclonal made from mixture of mouse and human proteins. This medication has been FDA approved for twenty years for certain B cell leukemias.
As early as 1987 physicians noticed that patients with both autoimmune leukemia and autoimmune disease recovered from both when infused with Rituxan. Rituxan has been successfully used in over ten different autoimmune disease and is currently being tested in many other autoimmune conditions.
Rituxan destroys the B cells which create the autoantibodies which fuel the autoimmune reaction. No B cells, no autoantibodeis, no autoimmune disease.
Downside of B Cell Depletion Therapy:
Patients suffer many adverse reactions at the initial infusion (but with each subsequent infusion there are fewer reactions).
B Cell Depletion therapy also destroys immune memory (ability to make protective antibodies) for diseases you are immune to for instance measles, mumps, rubella, whooping cough, etc. New childhood vaccinations are necessary after therapy is complete.
B Cell Depletion Therapy can also unlease latent viral and bacterial infections that are currently being surpressed by the immune system. These latent (silent and no-threatening infections can get out of control without B Cells producing their protective antibodies. The two most serious concerns are tuberculosis and worse a fatal virus called Progressive Multifocal Leucoencephlopathy (PML). PML is a very rare complication.

b) Ofatumuab (HuMax CD-20) is a fully human B cell depletion therapy in late stage clinical trials for B cell leukemia and autoimmune disease (RA). It is not yet approved to be sold to the public. It is thought likely to have fewer side effects than Rituxan because Ofatumab contains no mouse protein. The down side of Ofatumumab are the same as Rituxan because it is also a non-selective B Cell Depletion Therapy. In the future it would be nice to just target B cells that produce autoimmune antibodies and not the "good guy" B Cells that make protective antibodies. Ofatumumab is currently very, very difficult to obtain.

(2) Bone marrow manipulation (aka adult stem cell or hematopoietic stem cell) There are three approved methods for bone marrow manipulation. None works 100% of the time, but when the process works the autoimmune disease ends completely for months, years, and in some cases lifetime.
(a) Full replacement, full destruction of your own bone marrow (immune system) and full replacement—death rate 10 to 25 % in first year life time immune suppressant drugs their side effects and increased risk of infection
(b)partial replacement of your bone marrow sometimes called mixed chimerism or microchimerism bone marrow transplant. Much smaller amounts of bone marrow ablation chemicals and or radiation.Death rate falls dramatically, I believe around 5%.
(c) introduced bone marrow from another person with no chemo therapy or radiation in the recipient.

Other treatments/cures that have been successful in some cases are
(1) Intravenous Immunoglobin(IVIG)--but it takes a very large amount of (IVIG) to work, such large amounts can cause serious even fatal reactions due to other components in the bone marrow
(2) Cyclophosphamide partial destruction of your bone marrow with no transplant. Sometimes the “bad autoimmune part” is destroyed and when the remanents of your bone marrow grow back it is autoimmune free. (cyclophosphamide is liquid mustard gas as in WWI.) It’s value as a medicine was discovered during and after WWI.
(3) BCG vaccine Baccillus Calmette-Guerin. This is a vaccine used for tuberculosis in many countries. There is a documented association with less autoimmune, allergy and asthma for those who have had the vaccine. The vaccine has been used in mouse models with autoimmune disease and has ended it in the mice.
(4) Intestinal worms of various kinds—the one that has provoked the most interest is Pig Whipworms known as TSO (Tichuris suis ova) Intestinal parasites are thought to produce a homologue of anti-inflammatory cytokines in order to survive immune response in the intestines as a side effect this secreted homologue turns off autoimmune, asthma and allergy in some cases. The homologue made be similar to Interleukin 10 (IL-10).
Goat serum therapy—very weird but apparently legal for use in England for anyone who wants to try. Double blind trials underway so this is a very iffy one; however, one of the Osmond brothers (as in Donny and Marie—ask your wife) who has MS is using it (see This is MS website--<>

Most promising therapies in clinical trials
(1) Vaccines—there are three kinds
(a) desensitizing/tolerizing (aka allergy shot) the idea is to give the MS patient a very tiny amount of myelin (injection or orally) in increasing amounts until the immune system stops attacking the myelin sheaths surrounding the nerves. BIG NEWS is the VERY promising results for BHT-3009 made by Bayhill Therapeutics. It uses a bacteria RNA that encodes for myelin. LOTS OF EXCITEMENT in MS community for this one. There are several other companies working on a myelin vaccine as well.
(b) Traditional vaccine technique (as used in childhood vaccines) of which there are two kinds.
i. Whole cell vaccines consisting weakened autoimmune causing cells from the patient himself or someone else with the patient’s autoimmune disease. The cells used are cytotoxic T cells (T effectors) or dendritic cells. Lots of promise as a cure. The immune system learns that the cells are bad and destroys the ones introduced and all then the other similar ones of the patients own. Once destroyed by the immune system, the autoimmune process ends.
ii. Inflammatory cytokine called TNFalpha is the target of another vaccine being investigated by several companies. It is in clinical trials. The purpose is to get the immune system to eliminate the excess inflammatory cytokine.
(c) Vaccine that stimulate the immune suppressing part of your immune system. This vaccine stimulates a receptor on T reg cells. It causes them to divide rapidly. T regs are one part of the immune system that turns off autoimmune process. (the other known part is something in human immunoglobin hence the treatment option above #1 Other Cures.

(2) Multiple donor stem cells--(aka hematopoietic cells, aka mesenchymal cells) from MANY, MANY doners mixed together. This is being pioneered by Osiris Therapeutics. It is called Prochymal and is in clinical trials for Graft versus Host disease and Crohn’s. It has the potential of ending all autoimmune disease if it works. The idea is to get a healthy person’s immune system cells growing inside the patient and producing immune calming cells, immunoglobin, and cytokines. P

(3) Interleukin 10 genetically engineered lacto bacillus bacteria (the kind in yogurt and in our intestines). IL-10 is a cytokine that calms the immune system. Giving it to patients directly has side effects and does not work however in the small amounts that the bacteria produce in the intestines, it should great promise.

Intervening in the Cytokine Autoimmune Cascade
This is technique of action of the familar biologics that we use like Enbrel, Remicade and Humira as well as other biologics like Ankira etc. However, there are new drugs with new targets in that autoimmune cascade that may work even better if the FDA ever allows them on the market. These new biologics have completely different points of attack (or stimulate) in the autoimmune cascade. The idea of any biologic is to intervene in the autoimmune process to turn down the "bad" autoimmune parts and turn up the protective parts of our immune system.

Centocor's CNTO 1275 Ustekinumab that blocks IL 12 and IL 23 is very exciting. Rigel's R788 also looks promising. There are many many others in this category but they are still all in the overly lenghty FDA clinical trial process. Send an email to the Evil von Eschenbach, the current commissioner of the FDA and demand new therapies now.

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