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: <> 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