Tuesday, August 28, 2007

When cells die, the autoimmune disease dies

Apoptosis--a weird looking and sounding word but a word that could mean a cure for you, me and my son. It means planned programmed cell death. Apoptosis can lead to an autoimmune cure? Yes,indeed! In fact it could also lead to a cancer cure.

It seems both autoimmune disease and cancer have something in common. A major cause of both diseases is misbehaving "deaf" cells that were told to die for their misdeeds, but did not get the message.

Below is a link to an article describing a revolutionary new medication that provides the message to the "deaf" misbehaving cells. Once they hear it, they die. No more misbehavior. No more autoimmune disease. The disease process stops. In the case of cancer, the cancerous cells die leaving only healthy cells (tissue) behind.

This treatment is in clinical trials for MS (Multiple Sclerosis). In a year or two our lucky MS friends may have this new type of medication to turn off their disease. For all the other autoimmune disease sufferers who have a "less popular" form of autoimmune disease, there will be a long wait. In perhaps an additional five or ten years, we may also get access.First there will have to be years more of clinical testing for each individually named autoimmune disease. Then and only then can the autoimmune sufferers with less popular diseases get treatment. It is a shame that the FDA rules and protocols for clinical testing are so cumbersome.

My poor son has four autoimmune disorders, psoriasis, PsA, AS and a mast cell problem. Sadly none of them are as "popular" with researchers as the big four--MS, RA, Type I diabetes and SLE. I guess he will have to wait ten more years, if he survives. The poor FDA just cannot figure out how to change its snail like bureaucracy and unnecessarily cumbersome and complex regulations in time to alleviate his suffering and save his life.

Wednesday, July 4, 2007

Paul Welch-a brief bio

Paul on the right in a wild moment two years ago before his arms were so useless. Paul (May 2007) on far right excitedly trying to communicate with his brother who was visiting from the Bay Area and his mother. Paul communicates when he can with a whispered word or two and small hand gestures. Paul on left (May 2007) listening to his brother and mother talk but unable to enter into the conversation.

For any of you do have never met Paul.

Let me tell you of his wonderful belly laugh when he was a baby. The time he ran for treasurer of his elementary school and lost by three votes. Then the student who won did not want to do the duties of treasurer which was to sell pencils and erasers etc at little student store. Paul volunteered and did the job without the title He never complained. He never he felt slighted He just was his always helpful cheerful self. The whole school year he did the job.

At his large public high school, Vista High, he took every AP and IB class. He had nearly straight A’s. He had a couple of B’s, so was not valedictorian like his older brother had been. He didn’t care, not one bitter or sad or angry word. He had enough college credits from the AP courses to have nearly a year of college.

His SAT scores and grade point average were both above the median for acceptance at the University of California, San Diego where he applied as a HS senior. When he was denied, I called the placement office to find out why he had not been accepted. The woman I talked to confirmed the median scores for acceptance at UCSD and that Paul was above them. She told me UCSD had added extra criteria that year for acceptance. The new criteria took into account how many high school clubs the applicants had held a position of VP or President and the kind of clubs they were Some clubs were worth more than others. Paul had been on the debate team and in other clubs but was not an officier. Who knew that criterion would be added?

So Paul attended the local community college. He never even complained. It was just another opportunity. He entered the TAG program which guaranteed acceptance to UCSD if completed successfully. He had straight A’s for the entire two years at Mira Costa Community College, not one B or lower in any of his classes including three semesters of calculus.

He started dating a girl at the beginning of his sophomore year. She worked at the student newspaper, so he joined to. By Christmas he was editor.

When he got to UCSD, he excelled. He did get his first two Bs in college but he was still was scheduled to graduate Cum Laude until the last quarter of his senior year, the newly diagnosed PsA got too bad to be able to finish all course requirements and he had to take a couple more Bs. UCSD only counted courses taken at UCSD towards a Cum Laude so his grades for his freshman and sophomore year at Mira Costa did not count. No complaints from Paul those were just the rules.

He started in on a Master’s program at a closer college CSU San Marcos so he could live at home and we could help him with day to day routines. He found there were not enough handicapped parking spaces at CSUSM so he organized other handicapped students and spoke with the dean in charge. It took weeks yet in the end he got more spaces closer to the buildings for the handicapped. It had been a problem for those students for years. Paul solved it in weeks.

In December of that first semester in the masters program his fingers suddenly ballooned into sausages. He no longer could type. We got Dragon Naturally Speaking. In the many, many hours needed to “train” the program to understand him, he blew out his voice. It returned only briefly for about three weeks when he started the Enbrel.

Never, never, never did he complain. He just adjusted and accommodated with good humor. Now he is suffocating because his chest muscles are so stiff and sore and a medication which might help him is just beyond his grasp. Please share Paul’s story with anyone who might be able to help him get that medicine.

Contact me at darwindad@cox.net or pwelch2455@cox.net if you can be of help

Paul health has taken a serious downturn

Following is a series of cuts from various emails I have sent out over the last few days regarding Paul's very rapidy deteriorating condition. The picture of Paul feeding the ducks was taken at the Wild Animal Park in May 2004. He is weaing his Angel's baseball cap that he got at the Angel's game a few days earlier.


June 27, 2007
My son Paul seems to have taken a turn for the worse. You may remember he has PsA which was diagnosed in January of 2004. It has rapidly progressed. He cannot walk unaided talk or even hold a fork in his hand. We thought it could get no worse but it has. This last Sunday it started to affect his chest wall muscles. He has had several bad nights struggling to breathe. During the day his breathing is just ok, but at night he gets air starved and wakes up repeatedly.

June 28, 2007
It is 4 in the morning, Paul is bravely trying to lay down and let his mother sleep a little. His breathing is worse. All he can take is the shallow breaths because of the pain in the tendons or muscles of his chest wall. He doses then wakes up with air hunger. I feel like I am watching someone die. He has not been able to eat since breakfast yesterday. Each time he swallows he has to briefly hold his breath than breathe in sharply after. He is no longer capable.

I have never known Paul to complain without a reason. Usually he says nothing until he is in extreme trouble. It was that way when he contracted a whooping cough strain (age 9) that was not protected by vaccination. The pulmonary pediatric specialist who examined him was amazed he was functioning on so little lung capacity. Yet he never complained. He just went pale and white when he coughed.

I no longer can understand his very faint mouth movements or tiny, tiny whispers. His mother, Margaret was trained in signing and lip reading. She can still read his lips. He is now for the first time ever in his life saying to her “Mommy make it better” She is torn up. She says I would do anything if I could. I never heard him once ever say anything like that in his life before—not for pertussin, not for severe chicken pox. Not for any of his asthma attacks.

Margaret can not do anything for him. I have lied to her and said there is hope. We kept hoping Paul would get better, maybe this was asthma and would go away with time. Paul indicated no he did not think it was asthma. Each day but we kept thinking it would be better tomorrow. But it has not gotten better only worse.

I saw Paul’s grandfather in his last hours at age 87. He looked better than Paul does now. He could breathe. He could take in fluids. We and especially Paul have tried so hard to keep him out of the hospital. A chest cold with the current stiffness and soreness in his chest muscles would cause incredible pain. I feels like we are going to lose the battle to kep him out of the hospital.


June 30, 2007

Paul is back home from the hospital. He has inflammation of the lungs or tissue surrounding the lungs. The only treatment is inflammatories which give him quick severe asthma. There was nothing more hospital could do. >

His oxygen level is good but his problems expelling air make the CO2 level higher than his body likes. As you may know the body only senses CO2 not O2, so it constantly tells Paul he is suffocating even though he has enough O2.

He was better at hospital an able to sip some water and eat a few bites of pineapple, his only food today. Each time he swallows it hurts and feels like he is suffocating. He says, "remember the good times when I could breathe?"

We are upping the frequency of doses of his Enbrel. We will make an appointment with a rheumatologist to discuss a Rituxan transfusion, if all else fails. It is very expensive and risky as Rituxan is contains a lot of mouse protein. Seventy percent of patients experience reactions to the infusion. Rituxan is a back up plan due to the risks.

Paul is still quite miserable, but he is so tough. He deeps thinking about others more than himself--Mom the at me.What a man.


July 1, 2007

Paul had a much better night last night and slept several hours. He still feels like he is suffocating because he can no longer expand his chest due to inflammation. He is going to have to learn to breathe using only his diaphragm muscles.

I have had broken ribs. I know how sore they can be especially at night. There is no way to sleep on the side with the broken rib. Even little body shifts while sleeping cause intense pain that wakens you. Not at all fun. I believe Paul is having similar kind of pain now due to broken ribs on both sides. But the good news is he did sleep some. We all finally got some sleep.

He has also been able to drink water this morning and take down about a cup and a half of ice cream and yogurt. That is the most he has been able to eat since last Wednesday at lunch.


July 4, 2007

Paul only slept three hours last night. His breathing is better but he is wracked with pain. His sternum, wrists especially the left one, his frozen neck, his Achilles tendon left leg, and back constantly ache. There is little relief even with medication.

Good news is this morning he was able to eat about a cup of oatmeal and a whole nectarine. Of course it was cut into tiny pieces. Also good he has been able to regained use of his hand again to lift a plastic food to his mouth. He was able to feed himself today. He still cannot chew as the tendons of the muscle extending from his cheek bone to lower jaw are being affected.

Below his cheek bone is sore and swollen. His jaw now locks up for the first time ever. He is very sore in the sternum area and each swallow of food leaves him breathless as the food passes the sternum on the way to the stomach.

Saturday, June 16, 2007

The latest "Allergy shot" cure for MS

"Allergy shots" to cure autoimmune disese is in the News again. This time a protein target for MS utoantibodies has been found. When this protein is given in small amounts over time, the MS mouse immune system "learns" to ignore the protein and quits making autoantibodies. The mice get well. Here is the URL:

Below is a sentence taken from the article:

"When they gave injections of the protein to mice with the equivalent of MS, their paralysis was reversed. The protein restored order by suppressing the cellular processes causing the damage. Dr. Steinman speculated that the mechanism is tolerization, similar to the process used in allergy shots when a person with an allergy gets an injection of the protein that is causing problems for the body so it can learn to ignore it."

Allergy shot vaccines have the potential to cure ANY autoimmue disease. The only minor difficulty is identifying the exact protein target of the autoantibodies of that particular disease. However, identifying those proteins under attack is relatively straightforward using an autoimune patients blood serum, a protein microarray, and automated scanning. Once identified the protein would be given as "allergy shots" in increasing concentrations over a number of weeks--in six months no autoimmune disease.
When will it happen? Tomorrow if we work together, in fifty years otherwise. So many ways to cure you, to cure me, and to cure my horribly afflicted son; but not a one available for humans. To paraphrase an Anient Mariner, "Cures, cures, everywhere and not a one to use."

Wednesday, June 13, 2007

Grandma's diet gave me autoimmune disease

"your grandmother’s diet may still be affecting you today"

What your grandparents and parents ate long before you were conceived can determine how healthy you are today. Your grandma's diet could be the reason you are ill with an autoimmune disease. New discoveries in genetics show that genes can be turned off for generations by exposure to environmental chemicals. This new field of study is called epigenetics. The process of permanently turning off genes for a lifetime or more, even for generations, is called methylation.

What appears to be an autoimmune gene running in families could be simply an epigenetic change that happened in the lifetime of an ancestor. The genes for health are still present in affected family members just turned off. The discovery of methylation of genes has complicated the search for the autoimmune disease genes, but not stopped the search. In fact as these genes are discovered in families with true genetic causes of autoimmune, researchers will have a place to look for epigenetic changes as well.

Good news is that there are now three drugs approved for cancer therapy and an antibiotic (rapamycin) that will turn methylated genes back on. From the article referenced above: "three epigenetic drugs have already been approved by the U.S. Food and Drug Administration: Dacogen (decitabine) and Vidaza (azacitidine) are both demethylating agents that treat the pre-leukemic bone-marrow disorder myelodysplastic syndrome; and Zolinza (vorinostat) is used for treatment of cutaneous T-cell lymphoma. "

Turning genes back on should be a lot easier than giving us new genes with gene therapy. Reversing methylation is another promising area of hope for the cure of some autoimmune disease.

Tuesday, June 12, 2007

Response to NYTimes writer Gardiner Harris

Below is my letter to a writer,Gardiner Harris at the New York Times regarding his article about the FDA being to easy on allowing new medications to be approved. I disagreed.
Here is a link to his "news analysis" article:

Here is my response:
The problem at the FDA is the terrible length of time it takes for life saving drugs to get to patients. There has been a revolution in the development of medications for terrible conditions. Cancer and autoimmune disease are routinely cured in lab animals, but people cannot get these treatments.

Four years ago my youngest son, Paul, was a healthy college senior—dating, dancing, studying hard. He was a nearly straight A student at University of California, San Diego on track to graduate Cum Laude. He developed a “sprained knee” which did not get better with rest. It turned out to be the first symptom of Psoriatic Arthritis.

Today he can not get his own food or water. He cannot walk unaided. He cannot use a computer mouse. (He was once editor of his college newspaper). He cannot even talk as the arthritis has affected the joint that holds his vocal cords. Once he had a beautiful singing voice. Today his mother and I think it is a good day if he can croak/whisper ten words over the course of the entire day—mostly he kind of painfully and clumsily points to tell us of his needs. Once he was a superb athlete who ran everywhere and never took the campus shuttles. They were too slow for him.

Any of the following: HuMax CD-20, Centacor’s CNTO 1275, or Rigel’s 788 could cure him. All three work on different targets than the ineffective Enbrel he is taking now (cost $3000 a month). Any one of them could be a cure. But he will have to wait years to find out.

It will be at least another five to ten years for FDA approval of these for his particular form of autoimmune disease. He has an “orphan” autoimmune disease, not one of the Big Four—RA, Lupus, MS, or juvenile diabetes. The “orphan” autoimmune conditions get FDA approval of new medications only may years after the Big Four receive approval.

Even though every drug approved for PsA was first approved for RA, new RA drugs cannot get approved for PsA without another billion dollar clinical trial just with PsA patients. Few drug companies find it worth the cost for so few additional patients. There is no off label use of drugs either as the insurance companies will not pay for off label use and these drugs cost thousands to tens of thousands of dollars a MONTH! We might second mortgage our house and pay for a year or two but then we would be bankrupt.

Those three above are but three out of some forty plus cures I have found in the research literature on line. Paul cannot use any one of them, thanks to the FDA’s horrible rules governing experimental drugs. (Those cures are written about in previous posts on this Blog)

Researchers are terrified that if they allowed access to someone like my son and were found out, they would never get a grant again. It would be career suicide. So no mattr how promising the research or how much I beg and plead, those research cures for mice model of autoimmune disease will not get to my son.

HuMax CD-20 and CNTO 1275 are both in phase III testing. R788 is in phase II trials. Paul cannot qualify for any of those trials due to exclusion criteria. He has drug and food sensitivities. Yet the disease is destroying his joints and tendons and leaves him in terrible pain. When they are approved in five to ten years if he is still alive he will have many more crippled joints and still have food and drug sensitivities, so why can’t he try them now. R788 works on a pathway involved in drug and food sensitivities and might actually cure him of both PsA and the sensitivities. But Paul will not be able to get it.

Compassionate Use protocols are a joke. Virtually no one qualifies. If somehow you do qualify, drug companies do not want to give medications to Compassionate Use patients because if anything goes wrong with the treatment of those very sick patients, the FDA counts it against the Investigational New Drug during the FDA’s approval process. Smart companies refuse Compassionate Use Exemptions.

I have watched my son’s productive life destroyed. His disease will also end this painful crippled life he now has in the next few years because the same inflammatory process that has crippled him is destroying his arteries and putting him at great risk for a heart attack. He will die in pain, a prisoner of his own body, while we wait for the existing miracle drugs to be FDA approved.

See the Abigail Alliance website at: <http://abigail-alliance.org/> Read a few of the horror stories of dying patients desperately trying to access medication. Join with us and advocate for changes in the FDA policy.

It is not that the FDA has been snookered by Big Pharma into approving medications that should not be. It is the FDA refusing to understand the difference in patient need between a new allergy medication and a revolutionary new cure for autoimmune and cancer. A “me too” allergy antihistamine can be approved leisurely, but drugs that are novel for dire conditions are different. They should be allowed to be used by the sickest and most desperate as soon as they clear animal testing. Do you realize tens of thousands of people die needlessly each year in the United States while being denied the use of these new miracle drugs?

If Paul did qualify for a trial, he would only have a fifty/fifty chance of getting the medication. Paul would have to quit his existing meds. He would have a 50% chance of getting a nothing placebo but not be able to take any other medication. On a placebo alone he would get worse. That is great news for the study, not so good for my son. He would have more joints lost and more pain.

We know the outcome of cancers and autoimmune disease. We do not have to do trials with half the dying patients denied any treatment while we ghoulishly record when they die. It is a bit Dr. Mengele, wouldn’t you agree?

My son’s great aunt died a horrible, long, struggling to breathe, death from Multiple Myeloma two years ago. There were cancer drugs which might have cured her in clinical trials, but she could not get them. Today they are available but “darn, she just got MM too soon to have access” according to the FDA. Her last twenty four hours she could not sleep because she could not get enough air to fall asleep even with supplemental oxygen. She died finally of exhaustion when she could no longer get her breathing muscles to respond. A slow agonizing death is what the caviler attitude of the FDA condemned Aunt Lyt to.

Please consider patients like my son and my wife’s aunt in the next article you write.
Peter Welch

Saturday, June 2, 2007

Diagnosing Autoimmune--cytokine profiling

Below is a reply from an expert in the field of immunology to my email asking why there are not better tests for autoimmune disease. In particular I wanted t know why cytokine profiling is done by researchers but not by doctors for their patients. (Cytokines are immune system chemical messengers that regulate our immune system. When there is too much of one or too little of another, we have autoimmune disease. I have put in boldface the key to why we cannot get better testing to determine if we have autoimmune and if it is progressing. The research community does not consider it reliable and repeatable. Of course skin prick allergy testing is
accepted yet it is only at best 60% accurate.

Dear Mr. Welch
Thanks for your note, as a father too, I can only imagine your frustration. We do measure cytokine expression, but it is not clinically robust enough to use. The key, I hope, will be in the genetics and correlating those measurement with cytokine and other immune measurements. Good luck, and rest assured that while it is slow, we are making progress.
"Famous Researcher," MD (name withheld)

Below is my original email to Dr. "Famous Researcher" to which he replied above. I have added boldface to the most important points. The bold face was not present in the original.

Dear Dr. Hafler
I just read and online abstract of your recent article in Nature Immunology. I have a question, if "alterations in cytokine expression have long been observed in individuals with immune-mediated disease," why aren't there clinical tests for cytokine expression?

My son has both psoriatic arthritis and a hypersensitivity/anaphylaxis disorder. I have a hypersensitivity disorder as well. Yet there are no tests to rule in or rule out what we have. My son's PsA was not diagnosed correctly until he started having psoriasis outbreaks. The arthritis preceded the psoriasis by months. First it was a knee sprain, then inflammatory arthritis, then rheumatoid arthritis finally when the psoriasis showed up he got a correct diagnosis--PsA. Shouldn't there be a cytokine profile test for each autoimmune disease and its variants? Why isn't there one?

Not to mention the hypersensitivity disorder which leaves us with syncope, urticaria, angioedema and sudden onset apnea. Why is there no cytokine test to identify who has hypersensitivity tendencies and who doesn't? The "allergy" skin tests are only about 60% correct giving many false positives and even false negatives. I had a false negative for penicillin that almost killed me later when I took penicillin confident I would not react. Where are the cytokine or similar profiles that would indicate that my son and I are missing some kind of "off button" that prevents hypersensitivity reactions?

Another problem is the clinical trial situation. My son and I never qualify for any clinical trials because we have had hypersensitivity reactions to so many medications and foods (exclusion criteria). Even if we did qualify half the patients are given placebos. So our chances are only fifty/fifty we would get help. During the testing my son would have to stop taking the two meds (Enbrel and Plaquenil) that he has not reacted to yet. So if he is on a placebo arm his PsA gets worse and worse.

Clinical trials as run today are unnecessarily cruel and drawn out. Many revolutionary treatments (like Rituxan) take ten years or more to get to patients. A lot of suffering and dying goes on in those ten years. If we could measure cytokine changes, there would be no need for placebo-patients. Researchers could gage whether the IND was valuable by looking to see if the cytokine profile was beginning to normalize. If it did great, the IND works. If the cytokine profile does not normalize than the IND is not doing its job--back to the lab bench.

Is anyone doing anything about getting better testing like cytokine profiles for immune related disorders?

I know you are busy. I appreciate your good work. If you do not have time to answer I understand. Sometimes I just get so frustrated. Four years ago my son was a healthy college senior with girlfriends, a college lab job, his own apartment and a goal to be a doctor. Now all that is gone, he has only a chair in front of the TV and his bed. He no longer can walk unaided nor get his own food or drink. Once he was editor of his college newspaper. Today he cannot use a typewriter or computer mouse.

I am so angry and I am so sad,
Thanks for any hope on the testing front you can give me.
Peter Welch


Thursday, May 10, 2007

Blocking Immune Signals gives "Stunning Results"!!

More good news on autoimmune treatments—new treatments in phase III testing are expected to revolutionize treatment strategies for autoimmune disease.
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=62755 and
These new treatments are not cures or virtual cures but they are better than anything we now have. They should make as big an impact on autoimmune disease as the introduction of TNF-alpha inhibitors—Enbrel, Humira and Remicade.

These new biologics are fully human monoclonals that block two immune system chemical signals called interleukin 12 and 23. The experimental results have been so good that the two companies involved are racing to get this product through clinical trials and to market. Whoever wins is going to make a fortune. Even the runner-up should get rich with the leftovers. For stock speculators, the companies are Abbott and Centocor (Johnson and Johnson).

Right now the companies are both using plaque psoriasis autoimmune patients in clinical trials. The “wow!” factor of showing before and after pictures of patients with cleared plaque patches has won out over the lure of more patients and more potential customers that the Big Four (RA, SLE, MS, and Type 1 diabetes) have in their favor.

This is great news for my son and others with psoriasis, not so good for the rest of you. However, now that Big Pharma has figured out that a treatment for one autoimmune disease is a potential treatment for all autoimmune disease, I feel confident that this new monoclonal will be quickly tested on other autoimmune diseases.* Johnson and Johnson’s division, Centocor made too much money qualifying Remicade for just about everything while Abbott and Amgen sat on the sidelines. Abbott will not let that happen again.

This treatment while potentially revolutionary will not be the final cure we are looking for. It does block the inflammatory process farther upsteam than TNF-alpha inhibitors. This is good news. The closer to the beginning of the initiator of the autoimmune cascade, the more likely the biologic will be to have greater efficacy and fewer side effects. However, what we all want is to shut down the cascade completely. These new biologics will not do that. The cascade will still be constantly trying to re-start. These medications to block IL-12 and 23 will needed to be taken for the long term. Once they are stopped, the autoimmune disease will return.

Better still than blocking Il-12 and IL-23 will be blocking or disabling “autoimmune, antibody producing” B cells. (See my blog entry: B Cells keep the autoimmune pot boiling) There are new medications which will do that coming down the road in the next two or three years. These medications will need to be taken once a month to once every six months. They will have significant danger of infection and cancer and will not be a permanent cure. The first of these to be FDA approved for use in autoimmune disease was Rituxan. It is quite dangerous. There are better and less dangerous ones just around the corner—possibly FDA approved by about 2010. But they will not be a cure.

What we want is a permanent cure--something that turns off the cascade completely. Mice have these type of cures. We could too if we are willing to agitate and yell loud enough. Those full blown human cures to come will be with vaccines, fetal stem cells, or gene therapy manipulation of our own bone marrow. All three techniques have been successful at curing mice with autoimmune disease. Wouldn't it be nice to be cured? Wouldn't you like to be normal again? You could be if you are willing to yell as loud as AIDS patients did in the eighties.

What will you do today to get those cures to clinical trials?

*IL-23: a master regulator in Crohn disease - Nature Medicine
Indeed, several recent studies knocking out IL-12 and IL-23 subunits in animal models of inflammatory diseases such as multiple sclerosis and rheumatoid ...www.nature.com/nm/journal/v13/n1/full/nm0107-26.html

Cytos Responds!

I wrote to Cytos some time ago to ask about progress on their anti-TNF-alpha vaccine (TNFQb). The Cytos Director of Corporate Communications wrote back the next day with an update. I have posted her email below.

She says in the email that we can expect results from their latest clinical trials to be published between now and the end of June. I hope all goes well. Imagine having your own body produce the anti-TNF-alpha antibody. It would be so much safer, easier and cheaper.

Right now the cost of our son's Enbrel is $3000US a month. Lucky for us, my wife has family medical insurance through her work. Without her insurance we would not be able to afford the medicine. Her insurance covers only part of the costs of his medicine and physcian appointments. We still pay several thousand dollars a year for those costs. But without her insurance, our costs would approach forty thousand dollars a year. We would be bankrupt in a year or two.

Here in the US, if you cannot work at a place with family medical coverage, you cannot afford most medications. We do not have universal health care like the rest of the industrialized world. Very sad.

It takes a lot of money to buy TV ads in US. The candidate with the most TV ads almost always wins. Only major corporations have enough money to donate to politicians to pay for those ads.

Big Pharma is the biggest corporate donor, followed by Big Oil and major insurance companies.

Politicians who want to be re-elected must pass the legislation that Big Pharma and other big corporations want. Therefore no control on drug price. No universal health care that would put insurance companies out of business. Regulatory agencies that were created to protect ordinary citizens are now all run by mangers and lobbyists on loan from major corporations.

The Cytos email follows:

Dear Mr. Welch,

many thanks for your e-mail and your interest in our vaccine TNFQb. I have summarized below the current status for this vaccine candidate for your information. I hope this is helpful. I will also put your address on file, if this is fine with you, so you will be getting the news on this product candidate in future.

In October 2004, Cytos initiated a combined phase I/IIa clinical trial with TNFQb. The randomized, double-blind and placebo controlled study includes 48 patients with moderate to severe plaque psoriasis and is designed to evaluate the safety, tolerability and exploratory efficacy of the vaccine. Three different dose regimens have been already tested in a first part of this study. Initial clinical observations obtained in December 2005 suggested that the vaccine candidate is safe and generally well tolerated. Furthermore, it was observed that the number of patients who mounted an anti-TNF-α-specific antibody response was identical to the number of patients scheduled to receive TNFQb (study still blinded). The antibody levels were found to decline over time in all these individuals. This is an important safety feature for an Immunodrug™ targeting a self-molecule.

In 2006, the second part of this phase I/IIa study was performed with 24 patients. The highest previously tested and well tolerated vaccine dose (i.e. 300 μg) was compared with placebo. The patients in this second part of the study have completed the treatment period and data management is currently in progress. Throughout the treatment period, no safety concerns were raised and all vaccine injections were performed as planned. The first phase I/IIa study results are expected in this second quarter 2007.

I am sorry that I can not give you more detailed results right now and I wish you and your family all the best.
With best regards,
(name withheld)
Director Corporate Communications
Cytos Biotechnology

Tuesday, May 1, 2007

Autoimmune Vaccine-Cytos Biotechnology

Cytos Biotechnology, a Swiss, company, is developing a number of vaccines that if successful could revolutionized the treatment of autoimmune disease, tobacco addiction, excess weight problems (metabolic disorder-type 2 diabetes), allergy, asthma, and eczema.

The autoimmune vaccine is meant to cause our bodies to produce our own antibodies to TNF-alpha. Instead of paying $1000-3000US a month to buy mouse and hamster antibodies o TNF alpha, we would make our own!

TNF-alpha is the chief immune system messenger causing inflammation. It is the main target of the biologics for various autoimmune arthritis diseases. The vaccine, if it works, will be useful for any autoimmune patient who takes Remicade, Humira, or Enbrel.

Cytos picked plaque psoriasis, probably because of the ease of visually assessing progress should the vaccine work. Pictures sell product. But just because Cytos started with plaque psoriasis does not mean the vaccine wouldn't help many (most) other autoimmune conditions.

Remicade is a mouse antibody that attacks TNF-alpha when injected into us. Humira is a fully human antibody that also attacks TNF-alpha. Enbrel is a Chinese hamster ovary fusion protein whose target is again, TNF-alpha.

The problem with each of these is that over time our body's own immune system starts to make antibodies against these medicines destroying them before they can destroy the TNF-alpha. The longer we take these biologics the less likely they are to work. Worse yet, for the ten percent of us who get hypersensitivity reactions, the longer we inject any foreign antibodies or proteins, the more likely we are to have a life threatening reaction.

The Cytos vaccine gets around this problem by stimulating our own immune systems to destroy TNF-alpha with our own antibodies. Good idea.

Now the bad news, clinical trial results for phase II use of this anti-TNF-alpha vaccine were supposed to be announced last fall. A quick Google search finds no mention of these results being announced. Why? Did it take longer to register clinical trial subjects than anticipated, thus delaying the start of the trials? Did the vaccine fail to work? or Did it work too well?

If it worked too well volunteers may have had too high a rate of infections and cancers. TNF-alpha is crucial for the prevention of both. So while reducing the amount of TNF-alpha is a good idea, getting rid of all of it is not so good. Who knows what caused the delay? I have emailed Cytos to ask them these questions. We will have to wait for Cytos to reply. In the meantime, read more below.

Here is a summary of how the vaccine is supposed to work. It is from the Cytos website. Here is the URL:
Then skip down to the following:
"View information about the vaccine CYT007-TNFQb to treat psoriasis."
Click on this button: TNFQb Facts English or read part of the article below.

Proposed Mode of Action
CYT007-TNFQb is a therapeutic vaccine designed to instruct the patient's immune system to produce a specific anti-TNF-α antibody response that is able to neutralize the action of TNF-α.

This should prevent the binding of TNF-α to its receptors TNF receptor I or TNF receptor II, which are expressed by many different cell types, and reduce the subsequent inflammatory response.

In contrast to TNF-α inhibitors based on recombinant proteins and monoclonal antibodies, which have to be administered frequently and in high doses, CYT007-TNFQb represents an active immunization that is expected to have a long-lasting effect and thus allow for more convenient dosing schedules.

TNF-α, a cytokine predominately produced by macrophages, is a potent inducer of inflammatory responses and a key regulator of innate and adaptive immunity.

For its Immunodrug™ candidate, Cytos Biotechnology has selected an appropriate peptide of TNF-α that is directionally placed onto the highly repetitive carrier particle Qb (a virus-like particle) using the Immunodrug™ technology. The normally non-immunogenic peptide is now presented to the immune system in a highly organized array and has the ability to induce strong anti-TNF-α antibody responses.

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 http://www.immunetolerance.org/news/articles/pub_alerts/article_1222.html or
URL http://dx.doi.org/10.1016/j.transproceed.2007.01.070
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. http://louisville.edu/bucksforbrains/bios/ildstad.htm

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.

** http://www.eurekalert.org/pub_releases/2007-04/jaaj-ssu040507.php

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 Australian.com

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. http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel70.html

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 <pwelch2455@cox.net>