Sunday, April 22, 2007

B cells keep the autoimmune pot boiling

B cells in mammals have two main purposes. One, they make antibodies to fight pathogens (harmful viruses, bacteria, fungus, protozoans). Two, they retain immune memory of the antibodies needed to win previous pathogen battles.

If B cells incorrectly decide some part of our body is an enemy pathogen, then they make antibodies to label and to destroy it. These antibodies are no different structurally than any other good antibody. Because these antibodies cause attacks on your own tissue, researchers call them autoantibodies.

B cells also retain a memory of how to make these autoantibodies during remissions. B cells keep the autoimmune process going and they can restart it again after it is brought into submission by DMARDS, TNF alpha inhibitors (Remicade, Enbrel, Humira). If the B cells which make the auto-antibodies (and which retain the memoryo how to make them) are not eliminated, then the autoimmune disease you have can never end. Many new medications are on the way to destroy B cells or hinder their ability to make antibodies.

The B cells make the IgG antibodies that label a protein so that dendritic cells and macrophages know what to attack, engulf and destroy. If that protein is in a pathogen, good for you. If that protein is a part of your own body, you have autoimmune disease.

When autoimmune flares occur, these autoantibody producing B cells very rapidly increase. They are born inside your bones in the bone marrow. You may have felt the aching pressure in your wrist and lower leg bones caused by their rapid growth. I know I have.

I remember lying awake at night feeling the tremendous pressure in my wrists and mentally considering whether I could relieve the pressure better by smashing the bone with a hammer or drilling into it with my electric drill. Of course I did neither. Eventually the pain lessened. Apparently the rapidly produced "baby B cells" had left my bone marrow and had gone out to the mucous membranes of my intestinal lining. That migration resulted in less bone pain, but more gut problems.

Here is the URL of an article describing how autoantibodies produced by B cells are the key to the continued propagation of the autoimmune feedback loop:

B cells come in an infinite variety. Most kinds are very beneficial. They are key components of your immune response to pathogens and cancer. Killing all the B cells in your body makes you more vulnerable to infectins and cancer. You will even be vulnerable to childhood infections you previously had immunity to.

Sadly the only B cell medication on the market today is Rituxan which kills all B cells—both autoimmune causing ones as well as life preserving ones. B cell therapies that target only autoantibody producing B cells are still years away.

Rituxan has a very high rate of side effects as it is a mostly mouse protein (30-70%) monoclonal antibody. (Human cancer cells are fused with mouse cells to make it.)

There are fully human B cell killers (monoclonals) on the way. HuMax CD-20 is closest to being approved. Maybe FDA will allow it for RA in a year or two. All other autoimmune suffers must wait another five to ten years for additional clinical trials in order to use the fully human, HuMax CD-20. Our only choice today is to a chance on severe advere reactions and use Rituxan.

Rituxan is a short term answer at best. Almost all humans will eventually have a severe, perhaps, life threatening reaction to the mouse protein. Maybe not the first time or the second, but eventually, your body will notice the mouse protein and your immune system will go nuts. The doctors call that an adverse reaction.

Today you are not allowed to be infused with Rituxan unless you are “prep-ed” first. The prep-ing consists of a strong dose of antihistamine and prednisone. The idea is that if this is your time to react, you already have two of the drugs in your system that are used to try to stop adverse reactions. They are not always successful.

Reactions include gross swelling of body parts, whole body hives, sudden loss of blood pressure to the extent that no oxygen gets to your brain. The scientific terms for this are angioedema, urticaria, and syncope. The whole fun process is called anaphylaxis. It is very often fatal. If you survive the onset of symptoms, plan on these symptoms re-occurring for a month or more. Rituxan has been engineered to have a very long half life in your body.

At the beginning of the twentieth century when transfusions were the rage and doctors did not yet know about blood types, many doctors said, "Blood is blood is blood. If my patient needs blood it does not matter what kind I give him." So they tried giving sheep blood. It was blood after all.

All their patients died from adverse reactions to the sheep proteins in the sheep blood. It took quite awhile for doctors to fully understand that animal blood when transfused into humans, killed the humans. (It is actually our own immune system that kills us by over reacting to the foreign blood proteins.) For that matter transfusing blood from one mammal species to any other would kill the recipient mammal. So vets do not give dog blood to a cat unless they want the cat to die.

Today Big Pharma with a lot of money to be made says, "a monoclonal is a monoclonal is a monoclonal. " Thankfully the FDA is finally requiring black box labeling om some of these mouse monoclonals. Many, many patients have already died first.

Currently much of the FDA budget is provided by Big Pharma, so it takes a lot of deaths before the FDA will warn us of a problem with any blockbuster drug from a large pharmaceutical company.

Remicade is another mouse monoclonal. I see no reason for anyone to use it when Enbrel and Humira are available. Neither Enbrel or Humira has mouse proteins in them. Humira is a fully human monoclonal.

More on B cells later.

Revolutionary New Therapy for Inherited Diseases

In today’s news is an announcement from PTC Therapeutics of New Jersey that their lead drug, PTC 124, has been shown successful at reversing muscular dystrophy in mice.

MD is not an autoimmune disease. However, PTC 124 has the potential to treat a host of inherited, genetic diseases caused by nonsense mutations (in our genes—DNA). Some (many?) autoimmune patients could be helped.

In my opinion the following immune dysfunctions are most likely to have a gene malfunction that this compound could help—Crohn’s/colitis/IBD, mastocytosis/mast cell activation disease, anaphylaxis, angioedema (HAE), and severe forms of food allergies as well as severe asthma. Almost any genetic disease that runs in families might be helped. So my list could be musch too short.

PTC 124 is not gene therapy rather it helps existing genes that are malfunctioning to function well enough to end disease symptoms. It allows needed proteins to be made even when there is a nonsense mutation in the middle of a DNA sequence. It works in a similar way to the intravenous antibiotic Gentamicin but with less toxicity. It is administered orally—another plus.

It is already being tested on humans in phase II clinical trials for Duchenne’s muscular dystrophy and cystic fibrosis. Preliminary results look good.

The problem will be identifying the subset of patients who can be helped. Right now only genetic sequencing can be used in advance to determine who might be helped. Genetic sequencing is expensive and is not available for the vast majority of genetic diseases (like autoimmunity). However, if it is found to have a good safety profile, it might be tried on a “well it couldn’t hoit” basis on large numbers of diseases that might respond.

Here is a quote from the article:
"This new class of treatment has the potential to help a large number of patients with different genetic diseases that have the same type of mutation," says senior author H. Lee Sweeney, PhD, chair of the Department of Physiology at Penn. This genetic flaw causes from 5 to 15 percent (and in a few instances up to 70 percent) of individual cases of most inherited diseases, including DMD, cystic fibrosis, and hemophilia.

Don't get your hopes up for PTC124's quick use for our inherited, genetic diseases. This cure is decades away from use in the autoimmune community. If PTC Therapeutics allow PTC124 to be used in a large numbers of patients, they would jeopardize it’s possible FDA approval costing them millions of dollars. The company must carefully pick patients who are the most likely to benefit.

Here is why. If “risky” patients who do not meet inclusion criteria are allowed the medication under compassionate use exemption, the company must report any negative complications. The sickest at risks patients are the most likely to have complications. Those reported complications are used against the company during the final FDA approval process. It is contrary to a company’s best financial interest to allow much compassionate use.

There will be no expanded-access program for PTC 124. Here is what PTC Therapeutics says on the matter:
“At this time, an expanded access program would be premature. Although the early data in cystic fibrosis and Duchene muscular dystrophy are promising, the results are very preliminary, and were obtained from a small number of patients receiving PTC124 for a short period of time. Conduct of an expanded access program at this time might result in unacceptable risks for patients and might jeopardize the development of PTC124 so that it cannot become available for all patients who might benefit if its efficacy and safety are eventually proven.”

Why would expanded access (compassionate use) jeopardize the development (approval) of PTC124? Because of the stupid insistence of the FDA to penalize companies that are trying to do the right thing. Complications in patients who at most risk should not be counted against the approval of the new medication (IND). Those patients are dying anyway. At least give them a chance at a treatment. Give them some hope. Otherwise the sickest patients get new treatments last.

FDA rules must change if we are to get the cures in a timely manner. If you or your loved ones do not mind waiting in pain and dying quietly, then you should be fine with the FDA policy of penalizing companies for allowing for compassionate use. If you would like a cure NOW, perhaps you would be willing to call the FDA and complain. Let your US senators and Congress person know as well.

Saturday, April 21, 2007

Apoptosis in the news

A press release from Ohio State, today suggests another way to trigger apoptosis to get rid of troublesome cells that refuse to die. The Ohio State researchers have created a drug that triggers apoptosis by knocking out a ‘survival protein.’ Apparently some of us are sick because we have too much of this survival protein in certain malfunctioning cells that are slated for termination but refuse to die. The Ohio researchers are experimenting on cancer cells, but the drug should work just as well for autoimmune disease.

Some of us have immune cells that should die but don’t. I think of these cells as the “undead” staggering around in our bodies triggering all kinds of problems including some cases of autoimmunity. Make the “zombie” cells die and the autoimmune disease cascade ends.

Here’s the URL of the Ohio State article:

Here is another apoptosis drug in the news. This one was created by researchers at M.D. Anderson Cancer Center at the University of Texas.

When will it be tried on misbehaving immune cells? That is up to you. What are you willing to do? When will you demand that apoptosis drugs be used in autoimmune disease challenges? How loud will you yell?

Sorry no B cell posting until I can type longer. I am still having carpal tunnel issues.

Thursday, April 19, 2007

Mixed Chimerism autoimmune "cure" in the news

Below is an article describing a procedure that established a mixture of donor and patient bone marrow living together in the bones of autoimmune patients.

A few healthy bone marrow cells were added in a ‘gentle’ fashion to the bone marrow of autoimmune patients. While the donor cells lived, the autoimmune disease was cured.

Remember: all autoimmune disease is bone marrow disease; fix the bone marrow, fix the disease.

‘Gentle’ bone marrow transplants with ‘gentle’ treatments to make recipient bone marrow ready for adding bone marrow from a donor were done on patients with two seemingly very different autoimmune diseases—Pemphigus (blistered skin) and SLE (lupus).

“Gentle” means establishing some bone marrow donor cells mixed in among a patient’s bone marrow in a way that has fewer complications and deaths. This method results in far fewer problems compared to the traditional bone marrow transplant which is ‘harsh.’ Traditional bone marrow transplant means a complete destruction and replacement of patient’s bone marrow.

Pemphigus patients maintained both their own bone marrow cells and the donor’s bone marrow cells inside their bones. The two grew happily together for the over four years that follow up studies were done. The extra bone marrow cells from the donor cured the Pemphigus patients. Apparently they are still cured as you read this. Can anyone say life time cure?

Lupus patients were not able to maintain the donated cells in their bone marrow. When the donor cells died, their lupus came back. While the donor cells lived, the lupus was cured.

If the donor cells could be maintained, lupus could stay cured. (see my previous post on Dr. Ildstad and her amazing 'facilitating cells'. Yes, there is hope for a mixed chimerism cure for you, no matter your autoimmune disease if Dr. Ildstad is correct.)

Wouldn't you like to see massive testing of her technique. I would love to see my son run again.

What can you do today to make those cures happen now not later? Perhaps this partial list of things to think about doing might give you an idea or two.
Call the NIH demand more funding for an expansion of Dr. Ildstad to all autoimmune disease. Call the FDA demand loosing the rules for human clinical trials. Demand they fund clinical trials of potential new cures on a massive scale.
Call your US senator or US Representative and demand action from the NIH and FDA.

What are you willing to do now for a possible life-time cure?

Note: sorry no B cell cures blog today. I am having carpal tunnel issues. The B cell cures blog will be a lot of typing.

Key words for understanding article below:
Nonmyeloablative= “gentle” the patient’s original bone marrow is not completely destroyed. As opposed to myeloablative where it is totally destroyed and then replaced
Hematopoietic stem cell transplant (HSCT)= bone marrow cells from another person
Lymphohematopoietic=tissue which makes both the blood and lymph system [related to blood system, It is a series of “tubes” in your body carrying clear fluid (similar to fluid in blister)]
Chimerism=tissues of two different ‘animals’ mixed together

URL or
Transplant Proc, Vol 39, pp703-708, 2007
REVIEW: Hematopoietic Stem Cell Transplantation in Autoimmune Diseases: The Ahmedabad ExperienceVanikar AV, et al
Autoimmune disease represents a (AD) breakdown of natural tolerance against autoreactive antigens leading to a high mortality and morbidity. The reaction is usually polyclonal; T- and B-cell components of the hematopoietic system are responsible for disease progression. Allogeneic/autologous hematopoietic stem cell transplantation (HSCT) are the current modalities for treating drug-resistant AD.

Patients and Methods
We present a single-center retrospective evaluation of allogeneic HSCT with nonmyeloablative, low-intensity conditioning in nine patients (five males, four females) with pemphigus vulgaris (PV) and 27 patients with systemic lupus erythematosus (SLE; 3 males, 24 females). The mean follow-up period was 4.24 years for PV and 4.9 years for SLE. Cytokine-mobilized HSC from unmatched related donors, with mean dose of 21.3 × 108 nucleated cells/kg body weight (BW; mean CD34+ count, 6 × 106/kg BW) was administered in to the thymus as well as the portal and peripheral circulations of recipients. Cyclosporine (4 ± 1 mg/kg BW per day) and prednisolone (10 mg/kg BW per day) were administered for 6 months to protect mixed chimerism. A subset of patients with cross-gender donors were analyzed for peripheral blood chimerism at 1 month post-HSCT and every 3 months thereafter.

Sustained clinical remission with peripheral lymphohematopoietic chimerism of 0.7 ± 0.3% was observed in PV, whereas SLE relapsed after mean of 7.35 months of disease-free interval associated with fall in chimerism from 5 ± 3% to ≤0.08 ± 0.03%.

HSCT was effective to achieve early clinical remission of PV; and in SLE relapsed after a 7.35-month disease-free interval accompanied by a fall in mixed lymphohematopoietic chimerism.

Sunday, April 15, 2007

Dr. Ildstad's Universal Bone Marrow Cure

Dr. Suzanne Ildstad is the Director of the Institute for Cellular Therapeutics at the University of Louisville.

She may have made a discovery which will garner her universal acclaim as the discoverer of greatest medical advance since penicillin. If her discovery is as impressive as it initially appears, she will have a Nobel Prize in ten years or less. All of us in the autoimmune community should pray that she is correct. If so, we will have life-time cures.

She claims to have discovered a kind of immune cell (bone marrow cell) which could allow for the transplantation of adult tissues and organs from any human being to any other without the use of anti-rejection drugs or HLA tissue matching. She calls this cell a “Facilitating Cell.” (The medical research shorthand for her Facilitating Cell is CD8+/TCR-).

Her discovery would allow any patient with an autoimmune disease to receive bone marrow from any healthy, non-autoimmune patient. The donor blood marrow would be incorporated into the recipient’s bone marrow. With the help of Facilitating Cells, the two bone marrows could live contently without conflict.

That may sound easy. But it is not. Imagine putting young male Bagdad Shias and Sunnis, each one armed with loaded AK 47s, in the same dining hall and expecting them to sit calmly together to eat. Each Shia passing the serving bowls politely to the Sunni sitting next to him and vice versa. The chances of our Bagdad friends eating peacefully together are far higher than the chances of two different adult bone marrow tissues existing happily inside of our bones.

Yet, Dr. Ildstad says she has found a way to do just that. She says she can get bone marrows from different adults to co-exist contently together in the same bone. In fact she has known how to make bone marrows exist happily together since 1994! The year she first discovered Facilitating Cells.

Tissues from different animals living together happily inside of one animal is known as mixed chimerism.* If the process is perfected, it holds the hope of being a pemanent life time cure for most chronic diseases.

Dr. Ildstad’s technique would mean that a few healthy bone marrow cells living mixed in with our own might be enough to put a stop to the autoimmune cascade. Our own bone marrow cells apparently are unable to secrete the needed "stop" signal. A few of her facilitating cells would allow healthy donor bone marrow to live compatibly with our own. The transplanted bone marrow would control the cascade and restore immune tolerance (homeostasis).

Just think how a few signal lights and police officers giving tickets can change traffic chaos into a controlled and managed flow. So, too, would are immune responses be—controlled and managed.

It has been known for the last five years that giving a kidney (or any organ) transplant patient an infusion of the donor’s blood marrow can often greatly reduce or eliminate the need for anti-rejection drugs. Until now no one has understood why giving both worked better than donating a kidney alone.

Dr. Ildstad says she knows. If the donor bone marrow given to recipient contains “facilitating cells” then there is no rejection. Facilitating cells are very rare in the bone marrow. Sometimes giving a donor bone marrow infusion does not help. In those cases Dr. Ildstad’s facilitating cells were either not in the bone marrow donated or they did not survive. For organ or bone marrow transplants, the bone marrow must be “facilitator rich.”

Complete bone marrow transplants have been know to cure MS, RA, Lupus and autoimmune diabetes for more than thirty years.

The discovery was made by chance. Some patients with leukemia who needed a bone marrow transplant also had an autoimmune disease. In patient’s who survived the transplant, both the leukemia and autoimmune disease were cured. Physician’s were astonished and thrilled that the autoimmune disease was also cured. However, bone marrow transplant has yet to become a "best practices" standard of autoimmune treatment due to the high rate of "complications."

The death rate for a complete bone marrow transplant is still between ten to 25 % of patients who receive it. Many patients who do live, do not re-grow a fully functioning immune system from the donor’s bone marrow. They remain vulnerable to infections for the rest of their lives. The death rate among patients who re-grow only a partial immune system is many times the background death rate of adults of the same age. (A complete bone marrow transplant means the recipient’s bone marrow is completely eliminated in a process call ablation using chemicals like liquid mustard gas—cyclophophamide and whole body radiation.)

Because of the high complication rate an alternative to complete destruction of the recipient’s bone marrow has been sought for some time. Other researchers have tried partial destruction of the patient’s and letting the patient’s existing bone marrow grow back. The process has been called “rebooting” the immune system. This month researchers in Brazil and Israel announced they had “cured” type I diabetes in human patients using this process.* * The hope is that the malfunctioning cells in the bone marrow are killed and only healthy bone marrow grows back.

It is a random shot. The partial bone marrow destruction is not targeted to the malfunctioning cells because no one knows exactly where they are located. However, this technique (using low doses of cyclophosphamide) works more than half of the time. It is not new it has been used successfully in research centers in the United States for nearly a decade.

Some researchers have tried the partial destruction of the immune system with an infusion of donor bone marrow. Some times this process works and a cure is achieved some times it doesn’t and death results.

Dr. Ildstad’s work would allow for the partial destruction and implantation of donor bone marrow to happen much more safely. There would be no risk of rejection. There would be no deadly Graft Versus Host disease. Her technique depends on her claim that her “facilitating cells” are the magic mediators of mixed bone marrow conflicts. If she is right, a revolution in cures will happen. (Now we just need some “facilitating humans” to send to Iraq to stop the sectarian killing.)

Both the NIH and the Keck Foundation are impressed enough to have given her large grants to pursue this discovery. The NIH grant is for the development of a treatment for sickle cell anemia (another kind of bone marrow disease). The Keck foundation will finance “facilitating cells” as a cure for autoimmune diabetes.

Next planned blog entries include
(1) B cell cures,
(2) IVIG cures,
(3) new medications to correct malfunction immune cells,
(4) the need for a new AMA licensed specialty in immunity,
(5) the danger (for patients) of mis-informed physicians who were trained in last century’s medical schools,
(6) the problems with US medical insurance industry,
(7) problems with FDA clinical trial and approval processes, and
(8)the terrible burden of autoimmune on families and society.

*Mixed chimerism is actual not rare. Virtually all of us have a few our mother’s genetic cells living peacefully in and among our genetically distinct body cells. We may even have a grandmother’s cell or two. Our mother also has a few of our cells inside of her.

Every women who ever had a baby, had some of the baby’s cells cross the placenta and take up residence inside her.

The discovery of cross placental exchange of cells was made less than ten years ago, when healthy Y chromosome (male) cells were found in the blood of women who had previously given birth to boys. Decades later the Y chromosome cells were still alive.

At the time it was thought that this maternal mixed chimeric state might be one of the “irritants” that caused autoimmune disease to be several times higher in women than in men. Now many researches believe that mixed chimerism instead of causing autoimmune disease could cure it.


Friday, April 13, 2007

Russia to use Fetal Pig to treat auoimmune diabetes

Russia has announced a human trial of fetal pig cells to be used in an attempt to cure autoimmune (juvenile, type I) diabetes. The Russians are being heavily criticized by Western medical authorities (see this month's Nature).

We,in the autoimmne community, should support the Russians. We should demand similar fetal cell testing be done in Europe and the United States. We need more human trials of innovative new therapies not fewer.

Why? Read my previous post.

Also see article below printed in the Austrailian two days ago. It concerns a New Zealand man cured of autoimmune diabetes by fetal pig pancreatc cells ten years ago! The transplanted cells are still functioning today.

Had this technique been accepted and widely used ten years ago, my childhood friend, Barbara might still be alive today.

How many more of us must die before proven cures are widely recognized and incoporated as standard medical practice by the head-in-the sand Western medical establishment?

Pig Islets Still Producing Insulin After Ten Years In Diabetic Man
Linda von Wartburg11 April 2007

Ten years ago, Michael Helyer, a New Zealand man with type 1 diabetes for eighteen years, received a transplant of pig islets. Much to the surprise of researchers, the pig cells are still putting out insulin at this late date. In fact, it was Mr. Helyer who alerted scientists at Living Cell Technologies (LCT) that the cells were still functioning.

Mr. Helyer received the alginate-encapsulated neonatal pig islet cell injection into his abdomen in 1996, at age 41. By twelve weeks after the transplant, the islets were going strong, reducing Mr. Helyers need for insulin by thirty percent. Porcine (pig) C-peptide was detectable in his urine for eleven months. Although his insulin had returned to pre-transplant levels by week 49, improvement in control continued: his A1c at fourteen months was 7.8%, as compared to a previous 9.3%. After that, however, formal testing ceased until Mr. Helyer brought himself to the attention of scientists at LCT nearly ten years later.

When Mr. Helyer was given a laparoscopy at that time, abundant nodules were still seen throughout his peritoneum (the membrane lining his abdominal cavity). Biopsies of the nodules showed capsules containing live cell clusters, and the retrieved capsules produced a little insulin when placed in high glucose concentrations in a test tube. When Mr. Helyer was given an oral glucose tolerance test, it produced a small rise in insulin that tested out as pig insulin.

Scientists at LCT are just now set to begin a trial in Russia of such transplants. (See the article Pig Islets Soon Tested in Humans in our April/May issue for more information on that enterprise.) According to LCT, more advanced versions of Mr. Helyer's pig cell therapy, using neonatal pig islets encapsulated in an alginate gel, could be available within two years if the planned human trials are successful.

Sources: XenotransplantationReutersThe

Fetal Cells--a revolution of cures

This post is dedicted to the memory of Barbara, a child hood friend who bravely suffered horribly through forty years of autoimmune diabetes and its terrible complications.
What if there was a known way to give you a life time cure for your autoimmune disease? What if this cure had been known by researchers for most of the last decade?

Would you be angry if a procedure similar to a bood tranfusion could give you or a loved one a lifetime cure? This procedure could be done at any major hospital anywhere in the world. How angry would you be? How much do you want that cure? What would you be willing to do to get it?

Well, there is a known cure based on an amazing technique that relies on a fortuitous artifact in the early development of mammal immune systems. Early fetuses have no immune system. Their tissues do not provoke any immune response. They are invisible to virtually all mammal immune systems.

The technique works not only for all autoimmune disease but also for any blood borne disease (hemophilia, beta thalassemia, sickle cell anemia, pernicious anemia). Even more incredibly virtually any replacement organ could be grown inside your own body using this technique.

No anti-rejection drugs would be needed. No Graft Versus Host disease problems ever. (GVH is a rather gruesome death where transplanted adult bone marrow attacks and liquefies the tissue of the recipient—think Ebola-like symptoms). This technique allows any tissue (including immune forming tissue) to be swapped between any mammals.

In fact using this technique AIDS could be cured. That’s right AIDS cured for life--no need for ever having the AIDS cocktail again.

No way! What kind of hoax is this? Is this some kind of alternative medicine, Himalayan herb scheme?

No, it is no phony scheme and yes it is real.

It is possible to do all of the above and more. Early mammal fetal cell transplants are invisible to the host’s immune system. N one knows how why they are invisible, but it is a good thing they are. Otherwisethey would be rejected by their mother's uterus (womb) and fail to grow. Transplanting early fetal cells means No Host Versus Graft (HVG=rejection) problems. Also apparently there are no GVH problems either. The transplants must be done before the immune system develops in the mammal fetus. Depending on species, the transplant must happen before four to eight weeks of gestaion.

Let me quote from just one article found on Eurekalert (premier cutting edge science info site on the web). Washington University School of Medicine researchers “found that obtaining primordia early in the pig’s development rendered them ‘invisible’ to rats immune system, eliminating the need for anti-rejection drugs.”

What did that mean? Researchers cured diabetes in rats using pig fetal (primordia) tissue* without needing to use any anti-rejection drugs whatsoever. This is a permanent cure. Sit back, think about that. A permanent cure. No need for drugs ever. Diabetes cured and done.

In this case the researchers cured type II diabetes (not autoimmune), but the autoimmune diabetes has been previous cured in lab animals using fetal cells.

In addition, Pig fetal (primordial) renal tissue has grown functional, rat-sized kidneys that produce urine in the abdomens of rats. (Although a pig kidney is several times as big as an adult rat, the pig fetal (primordial) tissue grew into a rat-sized kidney when transplanted into a rat. I wonder what would happen if pig fetal kidney were put into a whale?)

Cow fetal tissue has been transplanted into monkeys to grow kidneys.

How could autoimmune diabetes and all the other 80 or so autoimmune disease be cured?

Simple all they need to do is to transplant primordial (fetal) hematopoietic (bone marrow) tissue into us.* The fetal bone marrow tissue would correct our immune system deficit and voila! we are cured. There are some complications.

(1) Degree of bone marrow replacement--Right now no one is certain whether our existing faulty bone marrow would have to be completely destroyed, partly destroyed or if any destruction would be needed at all. If our bone marrow error is minor, then just a few correctly function primordial bone marrow cells could reverse it. However if the error is major, then our bone marrow would need to be at least partially depleted (ablated) to make room for the new bone marrow cells. In some cases our bone marrow might need to be fully destroyed and fully replaced. A bit dangerous due to infection, but far less dangerous than current bone marrow transplants (aka adult stem cell transplants) because adult bone marrow stem cells transplants carry the risk of GVH.
(2) Choosing healthy bone marrow primordia—In the US we know that somewhere between 60 and 80% of adults do not have autoimmune disease. Fetal primordia would likely have a similar percent of healthy donors; however, we would want to increase our odds to closer to 100%. Be terrible to cure one disease and get another from the fetal cells
(3) Fetal cells where goeth thou? There is an unsettled question about where else in your body the fetal cells might migrate to. Could any end up in the testis or ovaries? Whose genetic child would result? This has not stopped traditional bone marrow transplants some of whose cells may be getting into ovaries or testes. (Point of interest, It was recently discovered, that you already have a few of your mother's cells surviving inside of you. We all do. It is possible that some of your eggs or sperm have your Mom's DNA, not yours.) No one knows the answer to where non-related fetal cells would go. Until very recently there has been no way to track the transplanted cells. So far neither of the two new tracking devices/techniques has been used to answer this question. But the will be soon put to that prpose, I am sure.
(4) the queasy factor I (animals)—Do I want some other animal’s cells running around in my body. In the case of AIDS, I think yes. Baboons do not get AIDS. They are immune. Maybe as little as a teaspoon of baboon primordial (fetal) bone marrow could be a permanent cure. Maybe more would be needed. The key is transferring baboon immune cells to people cures those people of AIDS.
(5) the queasy factor II (religious) Do I want human fetal cells inside me? Isn’t that the height of immorality? No, in fact it is just the opposite.
When our middle child died as a fetus twenty six years ago, my wife and I would have been comforted to know that some of his/her organs or tissues could have saved others.
Our lost was caused by a natural, spontaneous miscarriage. But perhaps it turn out that a miscarriaged fetus cannot be used—too much damage. What if my wife had been injured in a terrible accident and the fetus could not be carried to term? Would we have donated tissues and organs? Of course! Would it have lessened the loss? Absolutely. I would love to think of some part of that lost child alive somewhere, curing someone.
Because of the ability to expand fetal tissues in the lab, it might be possible for the loss of one fetus in a terrible accident to cure dozens, perhaps hundreds, and conceivably thousands of suffering people. I do not know about your God or your morality, but my God and my morality would not only condone but demand that I donate those tissues and organs.

Why haven’t these cures come? Mostly because you do not know they are possible. If everyone were aware of these types of cures, they would happen. One month of Iraq War funding gets the first cures to people in the next few months. If we took action now, the first fetal cell cures would be available before the years end.

It would take perhaps a little longer for autoimmune disease but hemophilia and sickle cell anemia could have permanent fetal cell cures before this Christmas (2007).

Treatments for replacement organs could be started as soon as proof of concept experiments were done in animals. Those who needed new kidneys, even new fingers, hands or eyes, could have them by Christmas 2008.

For the autoimmune community and for AIDS, perhaps a year or two would be needed. The problems of hidden viruses, the lurking fear of late stage GVH, and the questions of where all those fetal cells would end up—all have to be resolved in animal experiments first. We have the technology in place now to solve each of these questions. We just do not have the will.

If the research goes on as it is today in fifty or sixty years, these fetal cell therapies will be routine. But if we push hard, these fetal cell cures could be ours (autoimmune community) in under five years.

So sit back wait and hope for fifty or start making some noise and get these permanent life- time cures in the next few years. The choice is yours.

Alexander Fleming discovered penicillin in 1928. It wasn’t until the middle of World War II, fifteen years later that it became widely available. In those fifteen years how many thousands of people died needlessly of horrible bacterial infections?

How many of us will die before we demand the cures. We have recently lost Susan Butcher, four time Iditarod Champ and comedian Richard Pryor to autoimmune disease. Shall we watch mouseketeer, Annette Funicello die of MS? How many more must die? For the sake of your genetic relatives, for your own sake, demand that research cures be tried on humans now!

Next blog: Best hope cure—Dr. Suzanne Ildstad and her amazing “facilitating cells”

*Primordia are cells obtained before the pig’s immune system is turned on and before these primordia cells fully form organs. Primordia cells have already committed to becoming a certain tissue type that gives rise to certain parts of the body. They no longer have the freedom to become any part of the body like an embryonic cell, but they still have the freedom (plasticity) to become any one of several types of similar body structures. For instance renal (kidney) primordia can become every different type of cell and structure in the kidney and likely the ureters, bladder, and urethra but could not become a heart.

**Remember: Our bone marrow makes all of our immune cells. It is a bone marrow error that gives rise to our autoimmune disease. Fix the bone marrow, fix the disease.

Thursday, April 12, 2007

Stem Cell Autoimmune Cures

Stem cells are in the news lately what with the Senate passing a new stem cell bill that President Bush has vowed to veto without reading. Also their have been news reports of stem cell cures for autoimmune diabetes in Brazil and Israel.

Stem cell cures are very emotional subject for me. If President Bush had allowed for unlimited stem cell research and funding in 2001, I feel like my son might never have had to be crippled. I might be healthy enough to work again.

I am a fifth generation Republican. My great, great grandparents and great grand parents were prominent abolitionists who helped to establish the party. I voted for Bush the elder twice. But that was the last time I voted Republican. If I survive my current bad bout with my disease and live fifty more years, I doubt I will ever find a reason to vote for my party again. I feel too much angry. My son has gone through too much agony.

I also spent more than twenty years as a Sunday School teacher, Board of Christian Life Member (Sunday School Board), and Christian Scouting director (Caravans). I have been a member of the Escondido Reformed Church, the Porterville Church of the Nazarene, and the Community Church of Vista (Christian and Missionary Alliance).

But even if I were well enough, I do not know if ever would want to be a member of a church again. I would not even have put up Christmas lights last December except Paul wanted to see them. The take over of our churches, by the angry and hate filled Christians who promote ignorance and misinformation instead of Christ's message of forgivenss, tolerance and love, has left a bad taste in my mouth. These “little god” Christians who would deny cures for the sick and call it compassion, what horrible people they have become. What a terrible image they have given to Christians in this country. Jesus weeps.

Today I called a local radio station, KLSD, the hosts there were talking about the issue. I wanted to give them a personal story of the horror of a disease that might now be cured if Al Gore had take office instead of George W. Bush.

One of the hosts talked to me off air, I wrote him the following email in response. I am tired andvery drained from today's bouts of the "big D" and do not have enough energy to post about the many and varied ways stem cell research could help the members of our autoimmune community. Perhaps tomorrow I will feel better.

Here is my letter to KLSD hosts Stacy Taylor and Scooter:

Dear Stacy and Scooter,
Thanks you for discussing stem cell research on the radio today.

And thank you Scooter for talking with me off air. You asked what you could do for us. You even offered money. Thank you for the offer. Your offer was very compassionate, but unless I had enough money to fund the research that is needed, money will not help.

You two have a megaphone that those of us who are sick do not have. Use that megaphone to:
(1) promote all forms stem cell research,
(2) answer all the right wing talking points on stem cell research
(3) losen up the tight regulations that the FDA has in place that are slowing revolutionary new cures for people.
(4) advocate for universal health care.

Promote all forms of stem cell research—embryonic, fetal and adult. No matter the stem cell source, cures could be found. The fewer restrictions on research the sooner Star Trek like cures would be available to all.

A word on fetal cell research, my wife miscarried between our two sons. If some of the cells from that child (fetus) could have been used for a cure, we would have donated them. It is compassionate to donate organs, right? Why not fetal cells?

Up to six weeks or so a mammal fetus has no immune system. For some unknown reason this allows fetal cells to be transplanted to any other member of a species with no rejection whatsoever. In fact early mammal fetal cells can be transplanted into virtually any other different mammal species with no rejection.

Researchers at Washington University in St. Louis took primordial kidney tissue from pig fetuses and transferred it into rat abdomens. In the rat abdomen, the tissue developed into tiny rat sized kidneys (made of pig tissue) that filtered the rat’s blood and put out urine. This experiment was done over three years ago! Other similar experiments have been done with other mammal fetal cells as well and even earlier.

Think how many dialysis patients have died in the last three years. How many could have been saved if my middle child’s primordial kidney fetal cells could have been transplanted into those patients! My wife and I would have felt better as well somehow part of our child was still alive. Of course her miscarriage was twenty six years ago, those fetal cells are long gone. But why not use fetal cells from others today who miscarry.

(2) Answer all right wing talking points. Embryonic stem cell research must be done because currently only ESC’s can divide indefinitely. A researcher can grow as many as he/she needs, for as long as he/she needs.

Adult stem cell are genetically limited to as few as seven division and then they are done and they die.

Eventually research on ESCs will yield information on how to get adult stem cells to continue to divide but until the research is done adult stem cell lab work is limited by numbers and by the amount of time a line of adult stem cells can be kept alive.

Another point on adult stem cell research, one of the CON talking points is that there are seventy cures for adult stem cells none for embryonic. The adult stem cell cures they are talking about are mostly bone marrow transplants that happen to have a few blood and immune forming stem cells in and among the bone marrow.

Bone marrow transplants have been done for more than thirty years, only five or six years ago researchers discover that there were a few blood and immune forming stem cells (hematopoietic) in among the rest of the bone marrow. The CONS immediately started mis-labeling bone marrow transplants as adult stem cell cures. The seventy adult stem cures are not new. It is old technology given a new name by the CONS.

The second CON talking point is that ESCs treatments cause cancer. True there have been problems with early experiments with undifferentiated ESC’s but now that researchers have discovered some of the cues for differentiating the ESC’s, the problem is closed to being solved. Besides the idea was never to use ESC directly to cure patients, it was to understand them and their differentiation process. Once the process is well understood, cures using any kind of cell would come.

[The differentiation process takes one fertilized egg cell and makes every tissue and organ in an adult human. Researchers are now at the very beginning of learning how that process works. ESC’s are crucial for understanding it. Star Trek type cures will happen when researchers fully understand it.]

(3) Advocate for the loosening up of FDA regulations
Right now there are forty revolutionary therapies, virtual cures and full blown complete cures for autoimmune disease in mice. Only a couple are currently in human trials.

Each set of human clinical trials is estimated to cost one billion dollars under current FDA guidelines. Due to the cost risk exposure, Big Pharma sets draconian exclusion criteria for clinical trials to try to eliminate the sickest patients.

If they allow all patients to try new therapies, some of the sickest will have adverse reactions or die. Their deaths or reactions must be reported to FDA. The deaths or reactions are counted against the company when they apply for FDA approval to sell the new medicine or therapy. A billion dollars in clinical trials could be lost if too many of the sickest patients die. (Not that they weren’t going to die of their diseases anyway.)

We need Blind Compassionate Use FDA regulations. Negative results for any Compassionate Use patient who failed to qualify for the trial due to exclusion criteria should be blinded. The results should have no bearing on FDA approval process.

(4) Advocate for transferable universal health insurance. When my autoimmune disease worsened, I had to quit work. No work, no medical insurance. There are no private insurance companies that would now insure me with a pre-existing condition. My son was a brilliant student. He worked hard at school. He had scholarships and jobs which fully paid for his first two years in college. He never got in any trouble (not one bad report in his entire scholastic career). Suddenly he is hit with a genetic time bomb. He cannot work. He cannot get health insurance. Medications costs thousands of dollars a month.

If my wife could not work, we would have no insurance whatsoever. How would we pay the $3000 a month for his medications? As it is now, because he is only covered by one parent, we have to pay between $3-5,000 a year more than if I still had health insurance. On top of the forty thousand dollar a year hit we take in the difference between my disability pay and what my working salary would be.

Every year in October when health insurance is renewed we have to worry will he still be covered as a disabled dependent? How much more will “our contribution” to his health care be this year? Every year the rules change unilaterally and we have to “contribute” more.

As far as direct help to family, I may need help from you in putting pressure on a researcher at UCSD Cancer Center, Dr. Thomas J. Kipps. He has access to a medication that holds great promise for autoimmune disease and for some kinds of blood cancers (B cell). The medication is called HuMax CD-20. It targets and kills the B-cells which are a key part of the autoimmune cascade. Eliminate the B cells, the autoimmune disease stops.

There is a danger if I receive the medication. I could die of a hypersensitivity reaction or an infection. But I am turning into a skeleton right now--thirty pounds lost in three months. I cannot stop the weight loss as I cannot eat without severe even life threatening reactions.

I do qualify for his Dr. Kipps clinical trial of HuMax CD-20 for three reasons.
(1) He is using it in a clinical trial for B-cell cancer. In other research centers in the US it is being used for autoimmune disease but not here and not anywhere close.
(2) I have an autoimmune disease that results in severe hypersensitivity reactions (likely caused by B cells). If I took HuMax CD-20 and had a reaction, the company would have to report my reaction. My reaction would count against them during the FDA approval process which could come in about two years.
(3) Even though it is known that B cell reductions can stop virtually any autoimmune diseases- (MS, RA, Lupus, et. al.), not all eighty autoimmune diseases have been tried with B cell reduction. No researcher wants to be the first one.

Right now I am trying an oral tolerance therapy to try to get my immune system to accept eight more kinds of food. If it works, I can stop my immediate problem of weight loss.

My immune system is presently causing me to have nearly constant stomach flu and poison ivy type symptoms. Food tastes wonderful in my mouth and swallowing but once it hits the stomach and especially the intestines, I become really ill.

My immune system is either “blind” to the difference between harmless and harmful or it is locked in “super high on” mode.

It is my B cells who are mis-remembering the harmless foods as harmful. The B cells are sending out the signals and antibodies which cause the rest of my immune system to attack my gut when I eat. But if oral tolerance works, I can buy some more time. If not, I need access to HuMax CD20 or other similar medication in clinical trials.

Hu-Max CD20 is a fully human monoclonal that destroys all B cells. It is superior to the only current approved monoclonal (Rituxan) that destroys B cell. Rituxan is more than half mouse protein. Even patients who have never had adverse reactions to any other medication are having extremely serious reactions to Rituxan because mouse protein is easily recognized as foreign by the human immune system.

My son and I have a history of adverse reactions. Our chances with Rituxan would be poor at best. Even HuMax CD20 has a good potential to kill me. The older a person is the more memory B cells. My 24 year old son would have a much better chance. But I must try it first to make sure that a person with our adverse reaction genetics could take it. We cannot try my son first. He is already suffering too much.

Sorry for the length of this letter. You probably can only help with the first four general ways. If you kept talking about those first four on the radio, that will at least give me hope that help might come eventually for my son. If you feel you can help with the HuMax CD20, I can give you contact information for Dr. Kipps.

I am not sure how you could help on getting HuMax CD20 except to broadcast how difficult it is to get new therapies.

Thanks for listening
Peter Welch <>

Tuesday, April 10, 2007

Whole cell, T-effector vaccine for MS

Here is another kind of vaccine cure for autoimmune.*A1104584400000*B1175636057000*C4102491599000*DgroupByDate*J2*N1002598&newsLang=en&beanID=487787774&viewID=news_view

This should be even more effective than the allergy shot kind. See Cure 3 in my Best Hope posting for a similar vaccine cure from a different company.

In this type of vaccine, autoimmune “bad guy” cells are damaged and re-injected into patients with the goal of alerting the immune system to their presence.

Those of us with autoimmune disease have a tremendous number of these “bad guy” cells but our immune systems do not see them.

By taking some of them out, damaging them (the process is called attenuating), then re-infusing the damaged cells, something about the damage alerts the immune system. It not only kills off the damaged cells but now sees the undamaged ‘bad guy” cells as well. Our immune system once cued (alerted) goes on to destroy or disable all the “bad guys” that are causing the immune damage. Autoimmune attack stops. We are cured.

Again notice it is one of the big four autoimmune diseases that gets treatment first. MS gets a shot (pun) at a cure before the rest of us.

Remember all autoimmune disease are caused by a bone marrow fault which makes our immune system. Any cure for one autoimmune disease should work for all autoimmune diseases since all autoimmune diseases are the same disease at their core.

Any one of us with the 80 or so autoimmune diseases could have our T effectors extracted from our blood, damaged (attenuated), re-infused and we are cured.

It will not happen for decades, unless you act now.

By the way all that Tovaxin stuff in the article, just refers to a toxin used to damage the T effectors. Lots of toxins would work. Heck nuclear or even UV radiation would work. Why do you think psoriasis phototherapy works? Enough UV gets through the skin to damage a few of the T effectors and/or dendritic cells in peripheral capillaries to start alerting the immune system to a problem of too many “bad guy” cells. Sadly phototherapy by itself is not enough for most of us. But getting a tan might not hurt.

We need this whole cell vaccine as well as the allergy shot vaccines in massive human testing NOW! Call the FDA, demand this kind of vaccine be tested on all autoimmune diseases NOW! Demand all patients who request treatment be given it. Demand the NIH fund these vaccine cures NOW! Tomorrow is too late.

MS "allergy shot" vaccine in the news

Check out this URL.

The above link will take you to an article about an “allergy shot” kind of vaccine for MS, an autoimmune disease. This new therapy is for one of the Big Four autoimmune diseases that get all the new therapies (RA, MS, Lupus, juvenile diabetes).

The protein in the outer coating of the nerves under autoimmune attack has been identified for MS. It has been designated as MBP8298. A series of infusions with the dose of MBP8298 steadily increased will hopefully induce tolerance for the protein. Tolerance meaning that specific Tregs (autoimmune good guys) will be formed which turn off the attack and T effectors (autoimmune bad guys) will be turned down.

This same type of allergy shot vaccine could be done for any of the eighty other autoimmune diseases. The specific protein would have to be identified for each autoimmune disease and its subtypes—perhaps 500 to 1000 proteins. Using a patient’s blood serum, a centrifuge, a microarray with fluorescently labeled potential targets and a computerized reader; the specific protein target under attack for any autoimmune disease could be found in a day or two.

That’s correct, no matter what autoimmune disease you have, the target needed to make this technique work could be found in less than a week. A couple of months of this therapy and about 60% of you would either have no symptoms or greatly lessened ones.

Do not get your hopes up. This cure is not coming for you any time soon. Even our MS friends will have to wait three or four years. For the rest of us, it will be decades.

So you can sit in your chair and hope for a cure and suffer and die in the meantime. Or you can take action for yourself, your loved ones and the rest of us. Call your Congressman and Senators. Call the FDA—demand unlimited autoimmune vaccine testing now! on every patient who wants it! Call the NIH—demand funding for this type of vaccine.

If the autoimmune community had the will, this vaccine cure could be available to every one of us by the end of this year!

The Psoriasis protein target has already been found, more than a year ago. With this technique my son could have had one less year of pain and disability. Instead he rots in his chair every day trying to ignore the pain. Or struggles to sleep at night when every movement hurts. I m tried of waiting and hoping.

If you are only hoping for a cure, you are lost. Hope chokes. Hope sucks. Hope is a loser.

Only action heals. Take some kind of action today. Cures today! We cannot wait.

Best Hope Vaccine Cures

To understand this blog, you must know that in terms of autoimmune disease the more T-regulatory cells (T-regs) the better. T-regs are an autoimmune patient’s friend. On the other hand, T-effectors are autoimmune “bad guys.” T-eff are busy attacking the patient’s tissues and calling in other nasty immune cells to further damage the tissue.

T-effectors can be converted to T-regs and vice a versa. To get well we want the balance between the two pushed toward the T-reg side. Both are T cells, a kind of white blood cell. They both originate in the bone marrow.

Yesterday this blog was devoted to “allergy shot” autoimmune cures. Those cures try to induce tolerance by injecting tiny amounts of the target of the autoimmune attack into a patient over time. The goal is to increase adaptive T-reg population or to convert T-effectors into T-regs. The more Tregs or Teff that act as Tregs the more tolerance the patient’s immune system would have for the auto-protein under attack in the patient’s body.

It was only two years ago that Arne N. Akbar of the Windeyer Institute of London showed that this conversion was possible in a paper he presented at the Cancer Vaccines 2005 Conference. He showed that T-regs are not fixed in time and made only in the thymus (which completely degenerates by the time you are about 21 years old). Previously researchers had hypothesized that no increase in T reg populations could be created in patients who were too old to still have a thymus.

Dr. Akbar showed that patients older than 21 years can hope to get more T-regs. The “allergy shot” therapy being developed (too slowly) at UCLA is one way to do that. But it is not the only way. Below I describe even more effective vaccines to move the immune balance (homeostasis) toward the T-reg side. The most promising, the closest one to being a cure for all autoimmune diseases, is the one developed using p277 peptide by Dr. Irun Cohen at The Weizmann Institute of Science Immunology Department in Israel. More on that cure at the end of this blog.

You may which to skip the next few paragraphs that describe how autoimmue vaccine cures work and go directly to the highlighted cures at the end.

Following is a description of the four best hopes for vaccine cures for autoimmune disease. Several have been developed for cancer but may easily be applied to autoimmune disease. Both cancer and autoimmune disease share the similarity of out of control reproduction of maladapted cells that the immune system fails to notice and destroy. Many cancer treatments have good efficacy in the treatment of autoimmune disease as well. One example is methotrexate. It started as a cancer treatment, but today it is used for most autoimmune diseases. It stops out of control cell proliferation.

Autoimmune vaccines work in three ways. They can cause the death of the out of control immune cells. They can cause those cells to be converted to harmless or even helpful. (Most vaccines seek to turn up the function of T-regs and convert existing Teffectors into T regs). Thirdly they can stimulate extra production of "good guy" immune cells to turn off the autoimmune response.

In research jargon a T-reg is a CD4+CD25hiFOXP3+ T cell. A T effector is a CD4+CD25-FOXP3- T cell. In the autoimmune “good guy” cells, the CD 25 is up high and FOXP3 is working. In the autoimmune “bad guy cells,” CD25 is off and so is FOXP3.

By turning on CD25 and FOXP3 the very cells attacking your body can be converted from attacking and destroying your tissues into cells that are protecting and guarding those very tissues. This is so cool.

Conversion of T-effectors into T-regs allows for autoimmune remission. It is not an absolute cure. At some point the disease could come back. But it would feel like a cure. A patient could not tell the difference between a T effector conversion and a cure.

Back to the vaccine cures. When you have an autoimmune disease, your immune system
precursors in the bone marrow are producing way too many of a few kind of cells for
example autoimmune B cells. These "bad guy" B cells (aka memory T cells) induce your immune system balance (homostasis) to get out of whack.

These maladapted B cells produce autoantibodies that attack and label your own tissues as "the enemy". Such a large amount of labeled "enemy" cells inside of you causes the T cell population to be pushed toward T effectors and away from T regs.

Another cell that can be out of control is the dendritic cell. It can wrongly activate autoimmune B cells. A third kind of out of control cell can be mast cells which activate dendritic cells which activate autoimmune B cells which make autoantibodies and the autoimune cacade begins.

All three are bone marrow products. All autoimmune disease is bone marrow disease.

The out of control proliferation of B cells, T-eff cells, dendritic or mast cells can be slowed with DMARDS-methotrexate, Plaquenil, Arava, etc. DMARDS target cells that are
reproducing too quickly and cause them to die.

Or a vaccine can be used to get your own immune system to notice that one or two kinds
of cells are reproducing too quickly. This kind of vaccine is even closer to a cure than the allergy shot kind of vaccine of yesterday. This kind of vaccine offers hope for cures for both autoimmune and cancer. Once the immune system is cued to notice the out of control cells, the immune system eliminates them. This kind of vaccine cues the immune system. It stimulates normal immune system auto-correcting processes to function as they are supposed to and stop the autoimmune disease process.

Cure 1: At Stanford Medical Center skin cancer vaccines have been studied for at least the last five years. The brother of one of my college roommates is alive today five years after getting a diagnosis of incurable fatal melanoma. At Stanford he was given injections of treated melanoma cells from other patients with melanoma. His immune system first noticed that the foreign cells and attacked and eliminated the other patient’s melanoma cells. Somehow during the attack on the other patient’s cells, his immune system was cued to also notice melanoma cells. After the foreign melanoma cells were eliminated, his immune system went on to eliminate all of his own melanoma cells spread throughout his body. He is five years cancer free. Are you listening, Elizabeth Edwards?

A very similar therapy has been used at the Weizmann Institute of Science in Israel to cure autoimmune disease. The idea is to get your immune system to notice the autoimmune “bad guy” cells that have way over proliferated. Once the patient’s immune system is cued to notice its own “bad guy” cells, it will eliminate or convert them to harmless or even helpful cells.

Imagine my son with psoriatic arthritis. We find another patient with PsA, perhaps his cousin who also has PsA. Take some of the maladapted autoimmune causing cells from their blood and switch them. Give my son his cousin’s cells and his cousin, my son’s cells. Each of their immune system notices the foreign cells and eliminates them which starts a cascade that then eliminates or converts all their own autoimmune T-effs (or autoimmune causing dendritic cells). The PsA is stopped for both of them. They both walk out without their canes.

Cure 2: At Cedars-Sinai Medical Center in Los Angeles rather than using cells from a different patients, some of a cancer patient’s own healthy cells were taking out, grown and infused with a virus containing IL-23. IL-23 is an immune system signaling molecule (cytokine). The cells that were taken were not cancer cells but dendritic cells. Dendritic cells are supposed to notice out of control cell growth and eliminate it. For some reason, in cancer (and autoimmune)patients the dendritic cells fail to notice the out of control proliferating cells. The I-23 labeling of the dendritic cells allows the cells to "see" better. The dendritic cells suddenly can "see" the out of control cells. The dendritic cells then eliminate them. See "Combined therapies may boost immune response and long-term protection against brain tumors."

Virally altered IL-23 dendritic cell therapy could work for over proliferating immune cells in our bone marrow as well. Our dendritic cells should be noticing the over proliferation of the "bad guy" autoimmune causing cells in our bone marrow and elminating them. Dendritic cell immunotherapy should be tried on the bone marrow of autoimmune patients today not decades from now.

Cure 3: PharmaFrontiers is doing a similar trial with Multiple Sclerosis patients. They are using the patients own cells. This time however they are using T effectors. The researchers are extracting the T-effs from the blood of the patient. Multipling them in the lab. Then irradiating them to slightly damage the cells and finally re-injecting the slightly damaged cells. The patient’s immune system can then “see” these slightly damaged cells. The now cued immune system notices there are way too many T effectors in the blood and command them to change to T-regs. Voila! The autoimmune disease is as good as cured. In a tiny trial of 15 human patients, flare ups were reduced 92%. See “MS vaccine testing to start in the US” BBC News 2006/03/08”

Cure 4--BEST HOPE--The p277 cure: A true cure of all autoimmune cures may have been discovered by Prof. Irun Cohen of the Weizmann Institute of Science Immunology Department. He discovered a way to get any immune system to make more T-regs with a simple vaccination of a protein he discovered. The protein is called HSP60. He recently discovered that even a tiny fragment of it labeled p277 is able to shut down the autoimmune response. Vaccinations with p277 are being used currently in human trials in the United States and Europe for autoimmune diabetes.

Vaccination with p277 converts T-eff to T-regs. It should work for any autoimmune disease. See “The molecular mechanism of a diabetes vaccine revealed.”

Then why is it only being tested on autoimmune diabetes? Well because juvenile diabetes (aka type I or autoimmune diabetes), RA and MS affect many more patients than the other "orphan" autoimmune diseases. The more potential patients, the more potential profit. Therefore the big three autoimmune diseases hog all the best new medicines and therapies.

Sadly current western medicine practices separate autoimmune disease into the 80 different targets of the disease rather than recognizing the unity of autoimmune disease as one bone marrow disease that hits different targets in different patients. All autoimmune disease starts and is sustained by a bone marrow error. Fix the error, fix autoimmune disease.

Autoimmune patients with the most popular (common) diseases always get the good therapies first. That is why we need to push for The Three Musketeer Autoimmune Research and Clinical Testing Rule: One (autoimmune) cure for all. All (autoimmune patients) for that one cure. If we worked together the cures would be here in a year or less.

Cure 5: The last kind of vaccine I call an “Ant Poison” Antigen Cure” for autoimmune. It works like ant bait. In the yard only ants are attracted to the bait. Only ants and their colonies are killed. Other insects ignore the bait and are unharmed. The same principle is used in this kind of autoimmune cure. Only “bad guy” autoimmune causing cells are attracted to the bait. The rest of the immune system is left alone. This type of vaccine in cancer therapy is often called a Trojan Horse vaccine.

This vaccine would very selectively prune out only the autoimmune parts of your immune system. A cellular poison (or radioactive atom) is hooked to the autoimmune antigen under attack by the immune system. The idea is to eliminate only the “bad guy” B cells. The antigen must act as a super antigen that directly interacts with the B cell without dendritic cell presentation of antigen. This half bait (super antigen) and half poison vaccine would kill only the “bad guy” B cells that are producing the autoantibodies.

Without autoantibodies labeling parts of your body as “the enemy” dendritic cells would ignore those body parts that were previously under autoimmune attack, T-effectors would also ignore them, as would macrophages. The body parts (joints, tendons, skin, pigment, muscle, myelin sheath, etc.) would then heal. If T effectors are not simulated to attack, they revert to T regs and protect these tissues not destroy them. The dendritic cells and macrophages wander off to look for real enemies. Your joints, skin or whatever that was being attacked would suddenly get better. Autoimmune disease is over.

How many decades before we get these cures? Do you want to wait? Why not start massive human testing in six weeks for each of these vaccine ‘cures’ in all eighty types of autoimmune disease? Could some people be injured or die? Possibly but aren’t we being injured and dying now? At least we would have a chance for a cure. I would be willing to bet big money that far less patients would be hurt in an aggressive hunt for a cure then are being hurt and dying today from all autoimmune diseases combined.

Get mad. Take action. Demand aggressive human trials. Eliminate exclusion criteria from clinical trials. All for one. One for all! Cures today!

Next planned topics: Trojan Horse Cures, stem cell cures, clinical trials-why really sick patients can not get in, Physician inexcusable ignorance of current research and repulsive condescension to autoimmune patients, problems at the FDA that slow new cures to a crawl, need for a new AMA sanctioned medical specialty licensing for autoimmune and immune dysfunctions.

Monday, April 9, 2007

'Allergy shot' Therapy, an Autoimmune Cure?

Caveat: Here is one of my guiding principles, it should be yours as well: Any cure for any one autoimmune disease could be the one cure for all autoimmune disease.

With the above in mind here are three vaccines that could cure you tomorrow if we organized and demanded them, now not later!
All three of these vaccines have already worked in laboratory animals. While the researchers take two or three decades to go from mice and rats, to dogs and pigs then monkeys, then phase IA clinical trials, phase IB, etc, we are suffering and dying. Read the following and wonder why we cannot have the cures today.

First kind of vaccine cure is a kind of allergy shot. It is what the allergy doctors like to call immunotherapy. It is being developed at UCLA by Allan J. Tobin and in Copenhagen by Johnny Ludvigsson. Diamyd Medical ( andAviaraDx of Carlsbad, California are conducting phase II human testing for autoimmune diabetes (type I diabetes) using this technology.

Allan Tobin discovered the protein in the insulin producing cells (beta cells in the Isles of Langerhans) in the pancreas that are being attacked in at least some people with autoimmune diabetes. He and his Swedish colleagues are using small amounts of that protein to inject into autoimmune diabetic patients to try to get their immune systems to tolerate the protein and stop the attack on the insulin making cells in the pancreas. And it works!

Allergy shots therapy is left over 19th century medicine that was grandfathered in to modern medicine at the beginning of the twentieth century. It is based on taking “the hair of the dog that bit you” as a treatment.

Today researchers have discovered the probable reason it works. By giving very tiny amounts of the substance your body reacts to (an allergen), a tolerance to that substance builds for most people. It is now believed by immune researchers that the tolerance is achieved through the production of protective WBCs called T-regulatory cells (T-regs) or through the conversion of attack cells called T-effectors from attack mode to protective (tolerance) mode.

Tolerant immune systems do not react to harmless or self (auto)antigens. Tolerant immune systems can tell the difference between the harmless stuff all around and inside of us and harmful pathogens. Tolerant immune systems only attack harmful pathogens and do not get confused by anything else. We really want to encourage tolerance. Dr. Tobin's vaccine does just that.

Dr. Tobin is using the protein under attack (GAD) in autoimmune diabetes as an “allergy shot” to promote tolerance to GAD. Google: UCLA neuroscience research leads to a possible treatment for type 1 diabetes. (September 15, 2006)

How does allergy shot immunotherapy help others with autoimmune disease? If GAD is also under attack in your autoimmune disease, then the cure is yours as well.

What if the target of the immune attack is different and not GAD? Then we find that protein target and convert it into an allergy shot vaccine as well. The allergy shot therapy of Dr. Tobin would work for your autoimmune disease as well.

To find the protein (antigen, epitope) under attack in your body is as easy as drawing some of your blood and doing a little lab work. The protein could be found in a day or less.

Here is how. Use a centrifuge to isolate the antibodies in the liquid part of your blood, then test those antibodies against a selection of fluorescently labeled proteins from the part of your body under attack. A series of microarrays could be used with automated reading equipment to find the protein (antigen/epitope). Once the particular protein for your autoimmune disease were found, it could be used for your own autoimmune/‘allergy’ shots.

In a few weeks you would be feeling a whole lot better. Start this process today, by Christmas you are a different person--a person with a "toleratant" immune system. With any luck you could be in autoimmune remission.

But do not get your hopes up. It will not happen by this Christmas or next. It will not happen for decades even though it works in lab animals right now. Why? FDA regulations, researchers afraid of losing funding, old ninnies on Institution Review Boards, and regulations that encourage caution to the point of no progress rather than cures.

Think about being cured. Think about your loved ones being cured. Wouldn’t that be nice. But it will not happen until you get angry. Write to the FDA. Write to your local newspaper. Write to your Congressman. Demand this technology be put into widespread use, now not later! Demand all forty mice cures be tested on all autoimmune diseases today! not next decade.

My time is up for now. I have to go take care of Paul. I will post more about the other vaccine cures later. They are even more promising then the allergy shot cure. The other vaccines are likely to work on one hundred percent of us. The allergy shot autoimmune cure is not likely to work on all of us, just like allergy shots do not work on all allergy sufferers.

By the welcome new reader, Barbara Yodice, Founder of the Autoimmune Information Network. Check out her website: <<>>

Sunday, April 1, 2007

Paul at the Wild Animal Park, May 2004

My son Paul in May of 2004. This photo was taken three month after his diagnosis of Psoriatic Arthritis (PsA)--seven months after his first syptom hich was a sore right knee.

In the photo he is at the San Diego Wild Animal Park. He aways loved Cheetahs as a child. We were able to purchase tickets for a special behind the scene tour at the Wild Animal Park for his mother and him. The tour allows for a much closer interaction with the animals including cheetahs.

He is wearing the Anaheim Angels hat that he purchased at a Angel's game a couple of weeks before this outing. His best friends drove him to the game. It was a kind of farewell. A year before, he and his friends seem to be always out, almost every night. At the time I thought he was out too much, it might affect his grades. It never did. He was nearly a straight A college student at the University of California, San Diego. His friends had already seen a dramatic decline in his physical abilities after just a few months with PsA. They wanted to give him a fun outing. He did enjoy himself. It was the last time he was physically able to go anywhere with his friends. The Wild Animal Park and the Angel's game were his last major outings. Now he is a prisoner of his body.

Currently he no longer can do major activities as the pain in his neck and back is too great.

In the last two years, his only outings are for medical appointments.

The appointments are terrible ordeals that take hours to get ready for and days to recover from. His physicians show little understanding of his difficulties. He is not allowed to have online camera appointments wth them. They insist he come to their office. For each appointment, he must be laboriously and painfully washed and dressed and then suffer great disomfort no matter how slowly the car is driven. He has pain as the car goes over each bump and around each corner to get there. I wish a doctor could live one hour in his body. Maybe then they would have a little compassion.

Sorry to complain. The photo above was taken when Paul was at the beginning of his now devstating disabilities.It was taken before the full extent of the coming physical problems were known or even anticiapted. Weird at the time we were so depressed that he had to sit down in order to put on his shoes and that he had to be pushed in a wheel chair. It is a good thing we did not know how bad "The Horror" would become. Today if Paul could put on shoes by himself or even better tie them by himself, we would have such a huge celebration. Back then I was angry that the disease made him have to sit. How could I imagine he would lose all use of his hands and fingers. Perspective changes. The Horror never stops.

Never wish to see the future, the pain it holds is too much to bear.

Apoptosis! Die cell die! or at least de-methylate.

Die cell die!

Getting our maladapted immune cells to die and stop causing us trouble is on the cutting edge for autoimmune virtual cures. Cancer researchers are blazing this trail. They hope to get “rogue” cancer cells to die. Getting the cancer cells to die might cure at least some kinds of cancer. So far cancer researchers have the vast majority of funding to make this concept into a reality. But it is worth knowing for the autoimmune community as well.

Apoptosis is the fancy science term for the programmed cell death. What? Some of the cells in your body are programmed to die? We do not want our cells to die, do we?

Yes, indeed! One possible cause of cancer (and autoimmune disease) is a glitch in the built in cell death program. When body cells are malfunctioning, there are internal (and external) cell sensors that are supposed to cause the cell to commit apoptosis. Re-start the cell death program and the malfunctioning cancer cells will die. Cancer cured. Re-start the program for mal-functioning immune cells. They die. The autoimmune feedback loop is broken. No more autoimmune disease.

In the womb your fingers (and toes) were webbed like a duck’s feet. All the cells in the tissue between your fingers had to die, so you could use your fingers/hands for something besides swimming. They got the apoptosis command and now you can independently wiggle your fingers and toes. All the cells in your prenatal tail complete with nascent vertebrae (bones) were also told to die. Your brain was pruned as well. The pruning did not stop until you were in your late teens. Do you notice you do not think in quite the same way you did when you were twelve? Apoptotic pruning continues our entire lives. It is responsible for many of the changes that happen to our bodies as we age.

After your immune system recovers from an infection many of the extra immune cells needed to defeat the pathogen are supposed to die as well. If they do not, they stay around causing problems. Welcome to one of the triggers for autoimmune disease.

Apoptosis is a hot topic in cancer research. It seems cancer cells are also supposed to die, but they have a mutation in the final gene that causes the cell death process. Or the gene may not be mutated at all, but rather it has been turned off (by methylation). Thus the rogue cancer cell do not die. Instead they reproduce (proliferate) until they block up a vital organ. Then you die. If researchers can induce apoptosis in cancer cells then no more cancer. Here is a link describing just one of dozens of apoptosis drugs coming to market in the next few years.

You have immune cells that have proliferated when they are not supposed to. Those same cancer drugs that can trigger apoptosis in cancer cells, can also trigger apoptosis in maladapted immune cells. (The "bad guys" immune cells are a tiny fraction of your B, T, and dendritic cells. All immune cells are "born" in your bone marrow. All autoimmune disease is bone marrow disease.) There are some other problem cells in some of your joints and tendons that are stimulated to grow by the attack of your malfunctioning immune cells. If the "bad guy" immune cells would just die, then the stimulus for excess joint growth (in RA, PsA patients) would end. The autoimmune process would halt.

Another possible cause of autoimune disease is called methylation. Methylation is a new discovery in genetics (about ten year ago). It seems some genes can be turned off by zinc fingers on a methyl group. No one understands why genes are sometimes methylated (turned off). But important genes can be shut down at the wrong time e.g. the apoptosis gene.

The methylated or shut down genes can stay shut down for a life time or longer. The methylted genes can even be passed to offspring in the methylated, shut down condition. Some family genetic traits/diseases are caused by methylation. Descendents for several generations receive theshut down gene.

The study of methylated genes is called Epigenetics. It is above (epi) or on top of the genetic laws of inheritance we all learned in high school. (Remember Mendel and his peas?)

Our immune cells may be turned on all the time because the gene for turning it ‘off” has been methylated. If the methyl group is removed, voila! We are cured. There are currently drugs in development which will un-methylate genes. Those drugs are being developed for cancer but should have autoimmune therapeutic implications as well.

Or immune cells that have finished their job may need to die and do not because the final step in the apoptosis process is blocked. They stick around like the un-dead, causing big problems--think zombie movie.

Not everyone with autoimmune disease will have it because cells do not die or immune down regulating genes are not functioning. But for some of us pro-apoptotic and demethylating autoimmune cures are possible. There are a whole host of apoptosis drugs that have been developed for cancer. We should have access to them as well, but of course we do not.

Also there are demethylating drugs being developed as well. So far these drugs seem a little more dangerous then the apoptotic drugs. There is even a potential new drug that causes ‘rogue” cells to senesce. (It puts them to sleep so they do no more harm.) Think Star Trek the Next Generation episode with Piccard/Lucutis and the Borg.

We, in the autoimmune community, should have access to all of these drugs. I mean right now, not later. Cancer patients have ten times the access to new drugs that we do. Virtualy every drug that helps B cell cancr patients (CLL, non-Hodgkins Lymphoma, etc.) would help us. Stand up and yell about. Write a letter to your local paper today. Tell your federal officials. We demand the cures now!

Here are some titles of published work on the subject. Just google the title to read the article. Sorry I do not yet know how to link to URL’s.

New Concepts in the Pathophysiology of Inflammatory Bowel Disease: The Failure of Apoptosis of Immune Cells in the intestinal Mucosa. Annals of Internal Medicine January 2006
Sorry link address was too long, it will not highlight.
“Early results find activity in drug that turns on tumor ‘death’ receptors”

Here’s the arsenic cure. Arsenic in the right amount triggers apoptosis of cells that need to die. Too much and the whole body dies. “Ziopharm presents at European Society of Hematology Meeting: Updates ZIO-101 Clinical Development Strategy.”

A newly identified immunosuppressive protein in rheumatoid arthritisThe findings of a new study expose DcR3 as one of the factors culpable for RA's hallmark hyperplasia and its crippling consequences. - size 6.7K

AVN944 inhibits IMPDH and induces apoptosis-related biomarkers in patients with hematologic ...IMPDH is highly upregulated in most hematological cancers and solid tumors -- an essential role in cancer cell synthesis of DNA and RNA. ... - size 12.0K

Google ”EntreMed Panzem 2ME2”

For methylated genes, “Drug that switches on genes improves myelodyspastic syndrome treatment.”