Saturday, May 24, 2008

Lupus Rituxan B cell depletion therapy safe effective

B cell depletion therapy continues to be successful in alleviating or ending autoimmune symptoms in practically every autoimmune disease it is tried in. Too bad that Rituxan is full of mouse proteins capable of causing severe adverse reactions when infused into humans. Good news is the worst is the first infusion. Every infusion thereafter the adverse reactions symptoms lessen. The ONLY medication in the Physician Desk Reference (PDR) where the rate of reaction goes down and not up with each subsequent dose.

Adverse reactions seem to be caused by B cell antibodies; so as B cells are depleted the rate of adverse reactions goes down. Could B cell depletion therapy be an effective treatment for peanut and other food allergy? You would think someone would try it.

Hopefully HuMax CD 20 a fully human B cell depletion therapy will be approved by the FDA soon meaning this decade. Maybe with a new president we will get a more aggressive FDA commissioner. Let's hope so because a fully human B cell depletion therapy should make the "miracle" of B cell depletion safer and more available.

Rituximab Effective, Safe for Pediatric Lupus

Reuters Health Information 2008. © 2008 Reuters Ltd.

By Will Boggs, MD

NEW YORK (Reuters Health) May 20 - B cell depletion therapy with rituximab is effective and safe for treating children with refractory systemic lupus erythematosus (SLE), according to a report in the May issue of the Archives of Disease in Childhood.

"Rituximab actually is an impressively good treatment without major known side effects so far," Dr. Kjell Tullus told Reuters Health. "It is the new treatment that has impressed me most during my 35 years as a doctor, but formal randomized studies are needed to hopefully confirm our data."

Dr. Tullus, from the Great Ormond Street Hospital for Children NHS Trust, London, UK, and colleagues conducted a retrospective study of rituximab in 19 pediatric SLE patients treated in their hospital with two infusions, usually 14 days apart, at a dose of 750 mg/m per infusion.

More than half the children (10/19, 52%) experienced full recovery, 9 showed partial improvement, and 1 had minor symptomatic benefit after treatment, the authors report.
There was a rapid decrease in median BILAG (British Isles Lupus Assessment Group) scores from 14 to 6 within 1 month, followed by a significant decrease in BILAG scores at 6 and 12 months.

Two patients with renal failure who required renal replacement therapy experienced significant improvement in renal function within 3 months of rituximab therapy and maintained the improvement without renal replacement therapy for 18 months, the researchers note.

There were no acute adverse effects associated with rituximab treatment, though four patients developed uncomplicated herpes zoster 0.5 to 15 months after the treatment.
The investigators recommend rituximab "to everyone with a very severe, life- or organ-threatening disease and for children who have not had a full response to earlier standard treatment," Dr. Tullus said. However, "there is a huge need to do a proper international study to find the place for rituximab in childhood lupus."
Arch Dis Child 2008;93:401-406.

Thursday, May 22, 2008

Turn on a gene turn off autoimmune disease

HDAC may be the most important string of letters you have never heard of. You see HDAC's can turn on protective genes that were mistakenly turned off. What? Yes indeed sometimes an error occurs that turns off a gene that prevents cancer or autoimmune disease. In the absence of the products of that gene, a cell (particularly a stem cell) may give rise to a cancer or an autoimmune disease process.

It turns out that our genes are not fixed for our entire lives. The longer we live the more our personal set of genes (personal genome)changes. Environmental stresses (infectious disease, pesticides, flame retardants and other chemicals) change which genes are turned on and off during our lives. In fact identical twins are less and less identical the older they live.

Gene expression is the term used by scientists to indicate that some genes in a cell make gene products or express genes. While other genes in the same cell are turned off and do not express gene products.

Most of our DNA (which contains our genes) is turned off in most of our cells most of the time. It has to be other wise we would die. We cannot have a yard and a half long neuron extending from your back to the end of your big toe suddenly expressing the genes used to make a white blood cell that is less than one tenth the size of a period on this page. Every cell in our body has all the DNA to make any other cell in our body. Yet various cells in our body are VERY different.

A long skinny elastic muscle cell has the same DNA as do round globular fat cells and hard calcium covered bone cells. Very weird to realize that any cell in our body no matter what organ it comes from has all the genes needed to make every other cell in our body even to duplicate our entire body.

If most of the DNA in most cells was not turned off most of the time, we could not survive. The genes for muscle cells to function must be turned off in bone cells and blood cells etc. Imagine if our white blood cells needed to kill infectious agents (bacteria viruses) suddenly turned on their bone cell genes, they would grow a 'shell' of bone and be useless to fight off an infection. The infectious agents that our body's surfaces are bathed in would have a field day. They could eat us alive uncontested by white blood cells. Some kinds of leukemia kill because white blood cells never turn on the genes needed to fight off infections.

As we age, environmental shocks and stress interact with the process that turns off and on genes. Usually the process helps us better adapt to our circumstances. A famous case of changed gene expression was documented in the children born to women in Holland who were pregnant during the last year of the war when the Nazis starved the entire Dutch nation. It turned out that these children as they aged had many times higher rates of type 2 diabetes and other metabolic diseases than other non-starved populations. The gene expression of these children was changed in the womb.

The turned on genes in those Dutch children are not so good in times of plenty, but durning times of starvation, they provide a protective advantage. The children were pre-prograsmmed in the womb to survive in a time of limited food. Sadly the programming stayed that way, even when food supply increased after the war ended. These genes could have been protective had the food supply stayed limited but instead turned out to kill them early when food was abundant.

Today we are beginning to understand the process that turns genes on and off. Wouldn't it have been nice if we could have re-programmed the genes of the children born to starved mothers in Holland? It was not possible then but now we begin to see how it might work. HDAC is one of the first steps to get non-working, turned off genes to function again.

Cancer and autoimmune disease fit into a very large category of chronic conditions that we are NOT born with. Instead we lead perfectly healthy lives until suddenly our disease process starts. It seems logical to infer that one possible cause of this sudden expression of a disease may be due to a sudden change in our gene expression in some critical set of cells. Drugs like HDAC are one way to turn on protective genes and end the tryanny of autoimmune disease.

There are other ways to re-start protective genes which are non-functioning due to slight errors in the DNA four "letter" sequence. These errors result in the wrong gene products or no gene products being produced. Sometimes these gene products are crucial to preventing autoimmune disease. In these cases the gene is not turned off rather it is non-functioning in the protective sense. These other ways include the use of micro RNA's and drugs that allow ribosomes to read through an error. More explanation of these techniques and drugs in a future post.

The important point is that there are now many options to correct gene defects. We are no longer stuck with the our current gene expression. Genes can be fixed. Good genes can be turn on. Bad genes can be turned off. Even the mechanism for making protective gene products can be fixed.

HDAC's are one step in the direction of autoimmune cures. The following article is about turning on a gene that protects against prostate cancer. When the gene is incorrectly turned off prostrate cancer results.

***Notice their were two side effects--one positive one negative. The HDAC treated mice lived longer than mice normally do. (Increased life span whoopee!!)But in the not so good category, the testicles in the treated male mice degenerated temporarily durning treatment.

The article is from


Ohio State University Medical Center
Experimental agent blocks prostate cancer in animal study

COLUMBUS, Ohio – An experimental drug has blocked the progression of prostate cancer in an animal model with an aggressive form of the disease, new research shows.
The agent, OSU-HDAC42, belongs to a new class of drugs called histone deacetylase (HDAC) inhibitors, compounds designed to reactivate genes that normally protect against cancer but are turned off by the cancer process.

The study, conducted by the Ohio State University Comprehensive Cancer Center researchers who also developed the drug, showed that the agent kept mice with a precancerous condition from developing advanced prostate cancer.
Instead, the animals either remained at the precancerous stage, called prostatic intraepithelial neoplasia (PIN), or they developed benign enlargements of the prostate called adenomas. The main side effect of the treatment was a reversible shrinkage of the testicles.

Of the animals not given the drug, 74 percent developed advanced prostate cancer.
The findings are reported in the May 15 issue of the journal Cancer Research. Human testing of the compound is expected to begin early next year.

“This study shows that an agent with a specific molecular target can dramatically inhibit prostate cancer development in an aggressive model of the disease,” says coauthor Dr. Steven Clinton, director of the prostate and genitourinary oncology clinic at Ohio State’s James Cancer Hospital and Solove Research Institute. “We hope to see this agent in clinical trials soon and ultimately used for prostate-cancer prevention or therapy.”

Furthermore, when the drug treatment was stopped after 24 weeks, two of the animals were followed for an additional 18 weeks. The animals developed adenomas but were alive after 42 weeks, well beyond their normal 32-week life span.

“The drug not only kept the animals cancer free, but also prolonged their life span,” says Ching-Shih Chen, who led the drug’s development and the new study at the Comprehensive Cancer Center. Chen is also professor of pharmacy and of internal medicine.

A veterinary pathologist on the study, first author Aaron Sargeant, graduate research associate in veterinary biosciences, was intrigued that adenomas occurred in the treated animals. “Adenomas are not commonly found to be part of prostate-cancer development in this system,” he says. “This drug appears to shift tumor progression from its usual aggressive course to a more benign direction.”
For this study, Chen, Sargeant, Clinton and their colleagues used a strain of transgenic mice that develops PIN at about six weeks of age, then progresses to advanced prostate cancer by 24 to 32 weeks.

The researchers added the drug to the diet of 23 of the cancer-prone mice beginning at six weeks of age, when the animals develop the precancerous condition, and continued the treatment for 18 weeks.

They then examined the animals. Of the treated mice, one showed signs of early stage cancer, but 12 still had only the precancerous condition and 10 had adenomas.
In contrast, 17 of 23 control animals developed advanced prostate cancer, two had early stage cancer, three had the precancerous condition and one an adenoma.
Experiments using a nontransgenic strain of the same mouse – they do not develop prostate cancer – showed that the degeneration of the testicles that accompanied the drug treatment was reversible when the drug treatment stops.

Chen noted that 186,320 cases of prostate cancer are expected this year, with 28,660 deaths from the disease. “Our findings are very exciting, considering that an agent capable of reducing prostate-cancer risk by only 10 percent could prevent 18,600 cases of the disease in the United States each year,” Chen says.
Funding from the National Cancer Institute, Department of Defense, William R. Hearst Foundation and the Prostate Cancer Foundation supported this research. Aaron Sargeant is supported by a fellowship from Schering Plough Research Institute organized by the American College of Veterinary Pathologists and Society of Toxicologic Pathology Coalition for Veterinary Pathology Fellows.

Wednesday, May 21, 2008

Breast fed children are smarter

Not only in breast feeding linked to less autoimmune disease for the mother and less allergy and asthma for the children, now it has been tied to an increase IQ in children who are breast fed. See the following article from the New York Times:

May 13, 2008
Nutrition: Breast-Feeding Tied to Intelligence
In a large randomized trial of human lactation, researchers have found evidence that prolonged breast-feeding is associated with improved scores on some intelligence tests in childhood.
The results, published in the May issue of The Archives of General Psychiatry, appear to confirm those of previous observational studies.
Researchers in Belarus trained 8,457 mother-infant pairs with an extensive breast-feeding educational program, while a control group of 7,856 received standard care. At three months, 73 percent of the trained mothers, but only 60 percent of the controls, were still exclusively breast-feeding. By six months, exclusive breast-feeding had declined substantially in both groups, to 7.9 percent for the education group and 0.6 percent for the controls.
At 6 ½ years, the breast-fed group scored significantly higher on tests of vocabulary, word matching and verbal I.Q., although the differences in several other tests of intelligence were not significant. Teacher ratings of the children were consistently higher for those who were breast-fed.
It is unclear whether the differences were caused by a constituent of breast milk or by the associated physical and social interactions between mother and child. But the lead author, Dr. Michael S. Kramer, a professor of pediatrics at McGill University in Montreal, said the results could not be explained by characteristics of the mother or the way she related to her baby. “It’s the breast-feeding that’s doing it,” he said.

Wednesday, May 14, 2008

Artificial IVIG becoming possible

Big news, now there is a chance we could get the protection and cure of IVIG without the danger. See the article below:

UNH Glycomics Center Helps Identify Sugar Linkage That Could Lead To Better Treatment For Autoimmune Diseases

DURHAM, N.H. - Researchers at the University of New Hampshire Glycomics Center have helped identify a specific carbohydrate structure that confers anti-inflammatory activity to a glycoprotein antibody that could lead to improved treatment of autoimmune diseases like lupus or rheumatoid arthritis. The study, reported in a recent edition of the journal Science, was led by immunologist Jeffrey Ravetch of Rockefeller University.

The work revolves around immunoglobulin G (IgG), the most abundant antibody in blood plasma. Intravenous immunoglobulin (IVIG) has within it a trace amount of a very active material that is effective in relieving the inflammatory affects of lupus, rheumatoid arthritis, asthma, and other autoimmune disorders. But because of the trace amounts of active material, effective doses of IVIG need to be very high, frequently leading to unwanted side effects.

This study involved rebuilding the human IVIG into a fully active molecule with a slight modification to a carbohydrate residue. These carbohydrate structures are linked to the immunoglobulin and referred to as glycans, and on the tip of this glycan is a specifically linked sialic acid. All the sialic acid on IVIG was converted to the active linkage that confers anti-inflammatory properties.

Understanding and analyzing the exact structure of sialic acid was the contribution of the UNH Glycomics Center, headed by director and research professor Vernon Reinhold. The center has developed tools and protocols using multidimensional mass spectrometry to determine the structure and functional relationships of these carbohydrates. Reinhold notes that while most biopolymers are linear and thus relatively easy to sequence, bush-shaped carbohydrates have proved challenging.
"With sequential mass spectrometry, we systematically untangle this bush," says Reinhold. "We take it down to the trunk then try to put it back together to determine its structure."

Reinhold and Glycomics Center research scientist David Ashline helped Ravetch pinpoint exactly how sialic acid was linked, which let the researchers engineer a synthetic human antibody that mimicked the linkages in IgG, providing an IVIG with enhanced activity for treatment of autoimmune diseases. In the Science paper, the researchers report that when given to arthritic mice, the engineered IgG was about 30 times more effective than IVIG.

"Now that we know what the exact structure is, we can build on it," says Reinhold. "Just as once you know what the motor in a car is, you can modify and make it more effective, and in principle, if you know the antigen, you can build the antibody."

Beyond this work with IgG, the Glycomics Center is demystifying the carbohydrate connections in cancer that contributes to metastatic growth and in avian flu where sialic residues on airway surface tissues serve as doorways for viral entry.
"Carbohydrates are the glue that pulls things together, the cell surface matrix in which cells communicate, and they provide the connections for signal transduction. It's only been within the last decade that we've realized that such structures are critical for all kinds of biological function," says Reinhold. "Now that we can define precise structures, we can begin to understand their function. This structure-functional relationship will have a huge impact on our health in respect to immune regulation."

To read the abstract of the article, from the April 18 issue of Science, go to;320/5874/373.

Pregnancy and Breastfeeding Prevent Autoimmune Disease

It has been well known for more many years that women suffering from autoimmune disease often go into remission during pregnancy and for some months afterwards. The remission is thought to be caused by chemical signals from the babies placental cells which "turn down" its mother's immune system preventing the maternal immune system from attacking the developing fetus.

Intestinal parasites seem to use similar signals as well to turn down theimmune system of their hosts. Parasites that survive have been self selected for the ability to turn down the immune system's attack on the parasites without turning off the host's immune system completely. The parasites that were too successful at turning off the hosts immune system did not survive as the host would die of bacterial or viral infections. for the internal parasite to survive to reproduce lay eggs and pass on its genes for immune suppression the genes must be very selective. Pig whipworms (TSO's) are being considered for autoimmune and asthma and allergy therapies.

The developing fetus to survive must also have the same ability as the internal parasite to turn down the maternal immune system without turning it down "too much".

Now there is evidence that breast feeding for more than 13 months has the effect of reducing the chances of a mother ever developing autoimmune disease. Now what do we do for the men and boys?

See the article below copied from

Women who breastfeed for more ayear halve their risk of rhematoid arthritis

Women who breast feed for longer have a smaller chance of getting rheumatoid arthritis, suggests a study published online ahead of print in the Annals of the Rheumatic Diseases.

The study also found that taking oral contraceptives, which are suspected to protect against the disease because they contain hormones that are raised in pregnancy, did not have the same effect. Also, simply having children and not breast feeding also did not seem to be protective.

The researchers compared 136 women with rheumatoid arthritis with 544 women of a similar age without the disease. They found that that those who had breast fed for longer were much less likely to get rheumatoid arthritis.

Women who had breastfed for 13 months or more were half as likely to get rheumatoid arthritis as those who had never breast fed. Those who had breast fed for one to 12 months were 25 per cent less likely to get the disease.

The proportion of women breast feeding for more than six months has increased dramatically over the past 30 years. The authors concluded that it was difficult to say whether there was a connection between higher rates of breast feeding and a corresponding fall in the number of women affected by rheumatoid arthritis, but that the results of the study provided yet another reason why women should continue breast feeding.

Sunday, May 11, 2008

Summary of Current Autoimmune Treatments

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

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

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

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

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

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

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

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

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

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

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

Saturday, May 3, 2008

May 3 update

Paul continues to improve with Remicade (infliximab) infusions every six weeks. He can now move his head up and down and flex his spine a bit. He used to love to dance and now can "dance" a bit in his chair when he hears "good" music on MTV. His voice continues to improve. His knuckles are less red and swollen and he can bend his hands not freely but better than before. the large bump on his left wrist is slowly diminishing. All good news. He is also using Imuran as his DMARD. It has been six months with no adverse reaction. He was only able to use methotrexate for six weeks before a reaction and sulfasalazine for ten weeks before he converted.

I am so glad Paul has not reacted to the "mousy" part of the Remicade. We have been so lucky. I cannot wait until the fully human version of Remicade (Golimumab) is approved by the FDA (aka the F'ing DelAy). Even better will be CNTO 1275, Ustekinumab (anti-IL 12/23), with only one subdermal injection (no more infusions!) every three or four months. It has got to cost less than Remicade and it will be so much easier to use. No more hours spent in a doctor's office with the infusion slowly dripping into his veins.

How can we get those slow motion bureaucrats at the FDA to step up the approval process?

On the news all I hear is that the FDA is broken because they approve drugs with dangerous side effects like Vioxx and Bextra or that the FDA failed at monitoring faulty production of Heparin in China, but in my book, the real scandal is the horrible delays of revolutionary medicines caused by the FDA's underfunded and under performing bureaucrats.

Paul's "asthma" remains a concern but he is having fewer episodes than a year ago when his undiagnosed Ankylosing Spondylitis caused his rib cage to swell and start to freeze up. Hard to get a breath when your ribs don't move.

Paul's physician charges $6000 each Remicade infusion. Our family insurance is through my wife's job as a teacher. It pays "70%" as it defines 70%--usual and customary--which is their way of lying about covering 70%. They really only cover about 55%. My wife turned in the paperwork for the RemiStart program which is suppose to give us some help. Our physician gave us the paperwork. Hope we get some help. When I still could work and before Paul had any symptoms we never had money worries.

Paul just hummed "The hills are alive with the sound of music." He has not been able to sing or hum for over two years. Up until today the only music he could make was with his lips, teeth and tongue in a series of clicks and buzzes. But just now he was actually able to use his voice box again! Wow! We are so lucky to live in the first time in the history of humans when the effects of autoimmune disease can be reversed a bit. The disease process is no longer inevitably down hill. Now when do we get the real revolution. When do we get one of the forty some proven mouse cures for autoimmune? Ask the FDA commissioner, Andrew C. von Eschenbach .

I went through a couple of months of severe problems with my "intestinal difficulties" and lost about fifteen pounds. My lowest weight 150 lbs a couple of weeks ago was the least I have weighed since I was a high school sophomore.

I seem to have "converted" to an intolerance for yogurt and fresh fruit. I eliminated them and have gained back five pounds. It is tough to get enough vitamin C without fresh fruit, but it is nice to be able to eat again. Without this colitis/anaphylaxis thing I have I am sure I would be obese. So there is a kind of silver lining to the pain and discomfort.

Any way as long as Paul continues to get better, life is good.