Saturday, June 5, 2010

Suffering human are a "scarce social resource" that must not be jeopardized by allowing clinical trial access to all

I found an opinion piece by a couple of prominent bio"ethicists" telling why cures for the suffering and dying must be delayed. The sick and dying cannot have access to cures that rats and mice can get now. It is important really to let us suffer. Yes, very, very important. See if researchers who found cures for our diseases in lab animals were allowed to use them immediately on the sick who are begging for them, well then there might not be enough volunteers for the 'careful' clinical trials that make armies of clinical trial workers fortunes.

I stopped counting at 22 lab animal out and out cures or treatment as good as cures for autoimmune disease like my son is crippled with and have so limited my life as well. Yes 22 things a mouse can have that you I and my son cannot because those clinical trials need 'fresh meat' for their trials.

It would be different if the multi-billion dollar clinical trial industry allowed every patient in that asked to be in. But the dirty little secret of the clinical trial billion dollar industry is that they exclude tens of thousands of critically ill patients who have the illnesses they are testing for but who do not have the right inclusionary or exclusionary criteria (too young, too old, too long with the disease, too short a time with the disease, not every one of the symptoms, or having an additional disease as well as the tested disease, which is all too common for autoimmune patients, or you live too far away, or, or, or, etc.).

I know because my son has happened twice been rejected for clinical trials. Even though he had the right condition and we lived close by the testing center, and he was the right age, he did not have a lesion quite large enough for the study. There were dozens of other trials I did not even apply to because the inclusionary/exclusionary criteria were so specific, so tightly written that he had no chance.

But when the medication is approved by the FDA, everyone has access not just the ones who have those narrow inclusionary and exclusionary criteria. So why not test everyone?

Our bio"ethics" friends do not see the tens of thousands turned away. Nor do they care about their suffering and deaths. They see it as "ethical" to let the suffering continue because, hey, we have to have thousands of human lab rats so that the clinical trial folks can pick a few dozen lucky ones to get a chance at the new meds or treatment.

For thousands of years civilizations and cultures found treatments and cures for illnesses the old fashion way trial and error. Some folks died. True. But many more were saved when the right treatment and dosage was established. I would be proud to volunteer and if need be die, just for the chance that my son could get a cure a day earlier. Why should he live in misery when there are so many ways that might allow his immune system to function normally?

What does society gain by spending one billion dollars and ten years on each and every new medication that comes out? Nothing. The only ones who gain are the folks who work in the multi billion dollar clinical trial industry.

Every one else loses.

The patients lose a chance at years of healthy lives or living at all. Big Pharma loses billions on the trials which means obscenely high costs for new meds.

The last bill for my son's seven vials of Remicade was 7K!!! He has an infusion every six weeks. My retirement age wife must keep working, so we have insurance which pays ever lesser amounts--now about 3/4ths of the cost which is pretty much my entire disability retirement. Could the meds be cheaper if clinical trial costs were less? Of course!

No one gains anything from the current immoral system except those employed in the clinical trial industry.

In ten minutes you and I could put together a much faster and more ethical system that would still be safer than the age old trial and error method of the curanderos, witch doctors, and forest herbalists.

Simply designate an institution as the National Testing Center. Free the Center of all FDA slowdowns and all risk of lawsuits or liability. Only patients who signed extensive informed waivers allowed in. The place funded half by government, half by Big Pharma. The rights to profits from the cures divided into three. One part to the government, one part to the person(s) whose idea it was, one part to Big Pharma based on the percentage they contribute to the National Testing Center. All patients who volunteer, every one of them, allowed to participate in trials.

The only goal of the National Testing Center is a cure as fast as possible. No other agenda. Only cures. Safety is not as important as cures. Money is not as important as cures. Delays for playing double blind games not allowed (of course we must have some good tests to keep track of disease progression--perhaps T reg competence?) Nothing gets in the way of cures as fast as possible.

At this Center everything is tried. All the cures for the mice. Every idea tested. Also all patients encouraged to keep an open access online journal of what is happening to him/her--treatment symptoms, problems, discomforts, successes. Anyone, especially potential patients, allowed to read what is written on the on line blogs. Those who died have their name memorialized on a Wall of Heroes that is the first thing seen when entering. Everyone would understand the risks. But we would also understand the incredible heroism of those who were freely willing to die to find that ultimate cure.

There would have to be an adjudication court to decide what percentage of profits the various "idea folks" contributed to the cures, yet even here there are easy solutions and models to choose from.

So why don't we do this simple quick thing to end suffering and death? Incidentally it would likely make the United States the center for cures for the world. It would bring unprecedented wealth to our country. No more Great Recession, no more trillions in debt to the Chinese. Who could be against this idea of fast cures now?

The Clinical Trial billion dollar industry! And the "cover your ass" bureaucrats at the FDA who are terrified to say yes to anything novel or new. No one else. Well except for the two bio "ethicists", Jonathan Kimmelman and Alex John London, writing in the article in blue below.

Please note: I have added bold face to written lines in their opinion piece that I find most ethically challenged. Did you know for instance, that your sick and pained body is a "scare social resource" that must be preserved in pain for the benefit of the clinical trial industry? Or that "providing dying patients access" is not a "true measure of a clinical trials worth"? Translation providing access for the sick and dying makes money for no one under the current byzantine clinical trial system.

Clinical Trials and the Common Good
Testing Innovative Therapies Is More than a Private Affair

By Jonathan Kimmelman and Alex John London | Tuesday, June 1st, 2010

It’s a drama that plays out again and again wherever cutting-edge science meets mortal disease. First, researchers test a therapy that works miracles in animals. Expectant patients flock to those researchers. But then regulatory authorities and ethics committees prevent the researchers from offering the new therapy because of concerns about safety or the science behind the animal study.

Some critics view this as a perversion of medical ethics. What happens between dying patients and their physicians, according to these critics, belongs to them and them alone. They further argue that oversight and ethics are now impeding medical progress. We think these critics are wrong on both counts.

Clinical research is not a private act. It is, instead, a public activity. For one, it is aimed primarily at producing a public good: the knowledge communities require to address their unmet health needs. For another, clinical trials are much larger than private transactions between consenting patients and researchers. The development of new therapies is, in the end, a group endeavor: taxpayers support basic research, companies fund trials, academic medical centers provide the space and equipment, and scientists conduct the research. The true measure of a clinical trial’s worth is not whether it provides dying patients access to unproven medications, but rather, whether it produces a bountiful yield of knowledge that empowers future healthcare providers.

Trials of novel interventions often occur at the vanguard of science, and each stage in the process of translating basic research into clinically useful interventions depends critically on the quality of the information generated at prior stages. As a result, physicians and patients will often have a difficult time distinguishing strong studies from weaker ones. Physicians and patient-volunteers thus lack the ability to reward producers of strong studies by joining their trials and avoiding studies of lesser scientific quality. Oversight structures are necessary to ensure that studies are rigorously designed and that they will pass on valuable knowledge to the next link in the chain of discovery. They also help to ensure that participants, physicians, researchers, and investors can pursue their individual interests without compromising the social mission of the research enterprise.

Clinical trials that are unsafe, or that have a poor scientific justification, pose several threats to the kinds of cooperation needed to transform hard-won advances in basic science into improved care at the bedside. A string of disappointing clinical trials can lead sponsors and scientists to prematurely withdraw support from an otherwise promising area. Unexpected and/or mismanaged safety issues can sully the standing of an entire field and interrupt recruitment of talented researchers and investment from academic research centers.

Poorly justified or unsafe clinical trials also threaten a misallocation of scarce social resources. Patient-volunteers, for instance, are in short supply for many types of research, and fewer than 60 percent of National Cancer Institute-funded clinical trials are able to recruit enough volunteers to complete the study. It is a legitimate ethical concern if scientifically unsound studies draw volunteers away from studies that have greater merit. Another way that trials place demands on scarce resources is through personnel: trials require highly specialized medical expertise. Medical scientists who commit their expertise to weak trials are less able to contribute to other, more worthy research endeavors.

Unfortunately, medical research has a long way to go in terms of strengthening the scientific justification for testing novel therapies like stem cells, vaccines, or approaches involving gene transfer. Animal studies are often poorly designed, executed, and reported. In some cases, interventions are introduced into humans in ways that deviate from what was tested in animals. One recent study showed that preclinical researchers often do not publish all their animal studies, leading to significant overestimates of a drug’s effectiveness. It is not at all clear that oversight bodies and ethics committees, which focus on the willingness of researchers and patient-volunteers to undertake a study, do an adequate job promoting the scientific quality of clinical studies.

Policy proposals that would seek to loosen scientific standards so that patients can more easily access unproven therapies miss the point of research. To preserve the power of clinical research as an engine for scientific advancement, we must recognize that successful scientific innovation requires the sustained cooperation of myriad stakeholders and that the knowledge that results from this extended collaboration represents an important social good.

Jonathan Kimmelman is Associate Professor, Biomedical Ethics Unit and Department of Social Studies and Medicine at McGill University. Alex John London is Associate Professor of Philosophy and Director of the Center for the Advancement of Applied Ethics and Political Philosophy at Carnegie Mellon University

Tuesday, May 18, 2010

New evidence that incompetent T regs are a root cause of asthma perhaps allergy and autoimmune as well

We know from previous research that the T reg or"good guy" cells in folks with autoimmune disease seemed to be 'incompetent'. They appeared to not be able to turn off the inappropriate autoimmune reaction started by the auto reactive antibodies ( think tiny chemical guided missiles) produced by 'rogue" B cells and continued and increased by the 'bad guy' T effector cells. The autoantibodies label our cells as needing to be attacked and the T effectors enthusiastically follow their directions.

We think we know that T regs in folks with normally functioning immune systems seem able to tamp down the autoimmune reactions before they start.

Apparently those of us suffering from one of the 80 or so named autoimmune disease could use properly functioning T regs. Perhaps the T regs working as they should would be enough to stop disease progression. No one is quite sure, but it is beginning to appear more and more like that may be true.

Now we have evidence that malfunctioning T regs may be at the heart of asthma as well. It seems that folks with asthma have lots of extra T regs in their lungs. Far more than in the lungs of folks without asthma. This is what we would expect if the job of T regs was to settle down over active immune responses like inflammation in the lungs.

You see the T regs of those of us with asthma still answer the call to stop the autoimmune inflammatory damage but when they get to the correct site in the body, they are incompetent. They cannot do their job. Hence more and more T regs are called in by the out of control inflammatory signals being given off by the damaged tissue. Sadly no matter how many T regs arrive, they cannot do anything to help.

If a way could be found to fix our T regs with some form of the multiple ways we know to change gene expression than we might get competent correctly functioning T regs. Please God from my hand to your ear. Then at least some if not all asthma, allergy, eczema, and autoimmune disease might be able to be stopped.

That day is still a long way off. But heroic lab scientist keep chipping away at what we do not know so that one day we will know enough so no one has to suffer from these horrors again.

Below is an abstract of a study done by fine folks at the University of Manchester which found the extra T regs in the lungs of asthma patients thus linking a possible cause of asthma with a probable cause of other autoimmune disease. Note when they mention 'effector lymphocyte activity' they are talking about our old nemesis, the 'bad guy' cells, T effectors. T effs attack our tissues in autoimmune disease.

One might infer that some kind of plasmapheresis or shifting/sorting of our blood cells to eliminate T effectors would stop disease, but sadly the T effs may be just a different side of the same coin that is T regs. Eliminate T effectors and then our incompetent T regs would convert into competent T effectors. Some studies appear to show that T effs change into T regs and vice versa.

The likely problem that we, the afflicted, have with our immune system, then, is that our T regs somehow do not function correctly to stop inflammation in the T reg configuration, but when they are in the T effector configuration they can function to cause inflammation, tissue damage and the killing of pathogens.

Probably if the T effectors configuration did not function correctly we would have died of infection long ago. So instead of hating them for the pain they cause, we should be glad that they can function to stop disease. They just are like unruly guard dogs that attack everything friend and foe alike. Hopefully someday we will have a method to train them to behave.

Here is the abstract:

Chest. 2010 May 7. [Epub ahead of print]
Increased airway T regulatory cells in asthmatic subjects.
Smyth LJ, Eustace A, Kolsum U, Blaikely J, Singh D.
University of Manchester, NIHR Translational Research Facility, Manchester Academic Health Science Centre, University Hospital Of South Manchester Foundation Trust, Southmoor Road, Manchester, UK. M23 9LT.

BACKGROUND: Tregulatory cells (Tregs) may play a role in suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of CTLA4, and the number of these cells that are intra-epithelial lymphocytes expressing CD103.

OBJECTIVES: The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared to mild asthma and healthy controls. The secondary aim was to investigate BAL CD4+CTLA4 and CD4+CD103 expression in these groups.

METHODS: Airway lymphocytes obtained by bronchoscopy from healthy controls (6), patients with mild (15) and moderate to severe asthma (13) were characterised by multi-parameter flow cytometric analysis using 3 methods to determine the numbers of CD4+ Treg cells: CD4+CD25(bright), CD4+CD25+CD127-, CD4+FoxP3+.

RESULTS: %CD4+FoxP3+ Tregs were increased in BAL of patients with moderate to severe asthma (median 4.8%) compared to both mild asthma patients (median 2.5%, p=0.03) and healthy subjects (median 0.95, p=0.003). Similar findings were observed for CD4+CD25+CD127- Treg numbers, but not CD4CD25(bright). CD4+ CTLA4 and CD103 expression were raised in moderate to severe asthma patients compared to mild asthma and healthy controls.

CONCLUSIONS: The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, are increased in moderate to severe asthma. CD4+CD103+ intra-epithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.

PMID: 20453071 [PubMed - as supplied by publisher]

Monday, May 17, 2010

Keep on Cleaning Surfaces and Washing hands, MRSA Rates are up Ten Fold

Dangerous skin and surface transferred bacteria (MRSA being only one) continue to increase in prevalence (and much worse virulence) throughout the United States. With no new antibiotics on the horizon and the ones we now use having little or no effect the only measure to limit these resistant bacteria is ever more cleaning and hand washing.

Ten percent bleach solutions are the best for killing these bacteria on surfaces. Alcohol also is capable of killing many of these bacteria, but is not as comprehensive as bleach solutions. Ultra violet light (as in sunlight) also kills them. Soap and water does very little but spread them around on the contaminated surfaces.

Any surface touched by any human can harbor these bacteria. The bacteria can still be cultured from completely dry surfaces for weeks after being initially contaminated. Bare wood is the safest surface material as they seem to die rather quickly on wood. Plastic is the absolute worse. An eight week test with various materials including plastic, metal, wood and cloth found that there was no diminishment in infectivity on plastic over the eight week period. Dry cloth as in sheets, towels and pillow cases was also surprising capable of causing infections for weeks. It had been thought that bacteria died on linens and towels rather quickly. But in this test using MRSA they did not. Why they survive so long on cloth, is unknown. With plastic there seems to be a good reason for their extremely long survival. Apparently even smooth feeling plastic contains millions of tiny depressions in the surface that are perfect incubators for bacteria.

Door handles, computer key boards, desk tops, text book covers are all key areas that may contain these newly evolved antibiotic resistant bacteria.

Good luck out there. Keep cleaning commonly touched areas in the classroom and keep washing your hands regularly. (Even though soap and water mostly move the bacteria around on surfaces, they are effective on the hands as the soap lifts the bacteria and running water carries them off the hands to the drain.)

A good way to know if you have washed long enough is to repeat the ABC song in your head as you wash. Wash all surfaces on your hands especially the finger tips. Scrub hard you are using friction and lubrication to break the connection of the bacteria to your skin cells. Once the connections are broken and loosen by soap and friction, away go the bacteria. It seems that bacteria have millions of tiny villi on their surfaces that act a lot like Velcro, but soap loosens their hold on human skin cells. When you finish the ABC song you have probably washed sufficiently.

The number of children hospitalized with dangerous drug-resistant staph infections surged tenfold in recent years, a study has found.

Disease incidence increased from two cases to 21 cases per 1,000 hospital admissions from 1999 to 2008. Most infections were caught in the community, not in the hospital.

The study, which was published Monday in the journal Pediatrics, involved methicillin-resistant staph infections, called MRSA. These used to occur mostly in hospitals and nursing homes, but they are increasingly showing up in other settings among children and adults. Recent evidence suggests hospital-acquired MRSA cases may be declining while community-acquired cases are becoming more common.

The results are "a good example of how something that is not unexpected remains alarming," said Dr. Buddy Creech, an infectious disease specialist at Vanderbilt University who was not involved in the study.

The study involved 25 children's hospitals; the tenfold increase in hospitalizations probably occurred nationwide, said Dr. Jason Newland, the lead author and an infectious disease physician at Children's Mercy Hospitals and Clinics in Kansas City, Mo., and the University of Missouri-Kansas City.

Almost 30,000 children were hospitalized with MRSA infections at the hospitals studied during the 10-year period. Most had skin or muscle infections, and 374 of them died. Although NewlandMRSA caused those deaths, it can be deadly and is blamed for more than 18,000 deaths in children and adults nationwide each year.

The study didn't examine whether deaths or the severity of infections increased.,0,5579892.story

Saturday, May 15, 2010

Genentech offers real hope for ending allergy and asthma

I believe we have real hope for an effective long term way to turn off inappropriate allergy and asthma symptoms. Genentech which is among the largest biotech companies in the world if not the largest has announced they have discovered a way to not only differentiate the bad guy B cells that cause our allergic reactions but to selectively block the function of only these B cells leaving the rest of the B cell population intact. Since B cells make the antibodies that protect us from virus and bacterial attack (and possible death without them), it is HUGE news to have found a way to have selectively turned off just the "bad guy" B cells responsible for the "evil" IgE that makes so many of our lives so miserable.

Genentech is also a deep pocket company so it should be able to finance the extremely expensive, tortuously long and Byzantinely complex Food and Drug Administration required clinical trial ordeal. (FDA rhymes with delay.) Many potential cures for autoimmune and allergic diseases have been lost to patients by the "valley of death" caused by these immoral barricades the FDA puts between laboratory discovered potential cures and patients. Some of these delays seem to have to do with politics of Big Pharma and their real goal of profits, profits, profits. Delays that increase profits for Big Pharma are good delays. Since FDA derives significant funding from Big Pharma whatever Big Pharma wants, Big Pharma gets. But Genentech is a member of Big Pharma. As such their treatment might actually get through. Let's hope so.

Of course we have all been disappointed by past promises for good allergy treatments, Xolair comes to mind. I hope that Genentech is being truthful with their announcement in the prestigious Journal of Clinical Investigations. Some companies seem to over hype announcements like this--say for instance Osiris' Prochymal. So who knows? But I do believe there is real hope that our children may have truly effective treatments for allergies and asthma. Base on the article below, this Genentech breakthrough appears to be one likely candidate.

If this works for allergy and asthma, similar selective monoclonals might work for autoimmune disease as well. If we could only turn off the "bad" B cells that are making the auto antibodies which keep the autoimmune disease pot boiling, then the symptoms of the autoimmune disease would end. Go new science discoveries!


Eliminating the Source of Asthma Causing Immune Molecules

ScienceDaily (May 11, 2010) — Asthma and other allergic diseases are caused by inappropriate immune responses. Soluble IgE molecules, produced by immune cells known as B cells, are key immune mediators of these diseases. Therapeutic targeting of IgE in the blood can neutralize its effects and is an effective treatment for moderate-to-severe allergic asthma. However, this approach does not halt IgE production and patients need to be treated repeatedly.

But now, a team of researchers, at Genentech Inc., South San Francisco, has developed a way to specifically eliminate IgE-producing B cells, providing a potential new long-lasting therapeutic approach to treating asthma and other allergic diseases.

IgE-producing B cells express on their surface an IgE molecule that is slightly different to the IgE molecules that they secrete. The team, led by Lawren Wu, generated a therapeutic molecule known as a monoclonal antibody that targets the portion of human IgE that is contained in IgE molecules on the surface of B cells but not in IgE molecules in the blood. When mice expressing human IgE were treated with this monoclonal antibody, their levels of IgE in the blood decreased substantially as did their numbers of IgE-producing B cells.

As the monoclonal antibody provided mice with protection in a model of allergic asthma, the authors suggest that targeting IgE-producing B cells using monoclonal antibodies similar to those described in this study might be of benefit to individuals with asthma and other allergic diseases.

The research appears in the Journal of Clinical Investigation.

Friday, March 26, 2010

More Autoimmune hope, Re-vitalizing T-Regs

There was more solid hope in the medical news today for a universal cure for autoimmune. Of course the cure currently is for mice, not people. But the principle of getting the "good guy" cells, the T-regulatory cells, to wake up and work correctly could stop autoimmune in its tracks. T regs turn off the "bad guy" cells, the T effector's attack mode thus turning off the autoimmune rampage of those "bad guy" cells.

If this trick works in humans, it could end most kinds of autoimmune diseases and most allergy and asthma as well.

Of course if the T-regs function is turned up too high and they work too well, then contagious disease or immune system suppressed viruses might become a dangerous problem (Think of the fatal PML virus be re-awakened in some Orencia and Rituxan patients).

The article mentions this technique for Rheumatoid Arthritis but it should work for a subset of patients with virtually any autoimmune diseases with the possible exception of lupus (SLE).

Here is the article:
Finding a potential new target for treating rheumatoid arthritis
March 25, 2010
By enhancing the activity of immune cells that protect against runaway inflammation, researchers at NYU Langone Medical Center may have found a novel therapy for rheumatoid arthritis and other autoimmune diseases. In a new study published in the March 25, 2010 online edition of Science, the researchers reveal how treating these immune cells with an investigational drug wards off inflammation by holding a particular enzyme at bay.

"This is an unusual mechanism that could provide a potential therapeutic approach for the treatment of autoimmune diseases like rheumatoid arthritis or inflammatory diseases like Crohn's disease," says Michael Dustin, PhD, the Irene Diamond Professor of Immunology and professor of pathology at NYU Langone Medical Center.
The new study was spearheaded by Alexandra Zanin-Zhorov, PhD, a post-doctoral fellow in Dr. Dustin's lab, in collaboration with Juan Lafaille, PhD, associate professor of pathology and medicine, and Steven Abramson, MD, professor of medicine and pathology and director of the Division of Rheumatology. The research was supported in large part by a five-year grant from the National Institutes of Health Roadmap for Medical Research funding initiative, under its Nanomedicine Development Center Program.

Joint-destroying rheumatoid arthritis is generally considered an autoimmune disorder spurred on by the hyperactivity of conventional T cells that fight off infections, cancer, and other diseases. Within the past few years, researchers at NYU and other institutions have learned that other immune system components known as regulatory T cells counterbalance the tendency of conventional T cells to become overactive, thus holding inflammation in check.

These regulatory T cells exert their influence by communicating with other parts of the immune system. Through molecular detective work and powerful microscopy, the new study's collaborators found that an enzyme known as protein kinase C theta is only partly activated in regulatory T cells. When the regulatory cells are most active, in fact, most of the interfering enzyme is physically kept far away from the area important for cell-cell communication. "It's a very unique distribution," Dr. Dustin says. "In conventional T cells this enzyme is normally moved to the area where the cells are making contact. But in regulatory T cells, the enzyme is as far away as it can get from where the cells are communicating."

Based on that observation, the researchers began testing inhibitors of this kinase enzyme, including a molecule known as Compound 20 that had been in development by pharmaceutical company Boehringer Ingelheim. Surprisingly, the compound boosted the normal activity of regulatory T cells by about five-fold. The researchers found that specifically blocking the activity of the kinase enzyme augmented the natural tendency of the regulatory T cell to keep it out of the communication channels. Thus, the compound enhanced the regulatory cells' anti-inflammation activity.

The Yin and Yang of T cells in Rheumatoid Arthritis

In rheumatoid arthritis, either an abnormal surge by infection-fighting T cells or a dip in the activity of inflammatory-fighting T cells—or perhaps both—could cause the immune system to attack our own joints instead. "Therefore, if you have an abnormal and suppressed regulatory T cell function, you have enhanced potential for autoimmunity," says Dr. Abramson.

The researchers bolstered previous evidence for such a link by examining the blood of 25 patients with varying degrees of rheumatoid arthritis. "In essence, what we were able to show is that if you look at this regulatory T cell population in rheumatoid arthritis patients, it is abnormally low in function, and the sicker the patients are, the more depressed that cell function is," says Dr. Abramson.

The defective regulatory cells from these patients were revived in tissue cultures with this enzyme inhibitor, the study showed. "We could get them back to almost a normal level of activity, like what you'd see in a healthy individual," says Dr. Dustin.

The researchers also tested the Compound 20 inhibitor in a mouse version of Crohn's disease, which is characterized by intestinal inflammation. When the researchers treated the regulatory T cells with the enzyme inhibitor and then injected them into the mice, their anti-inflammation activity rose so much that they essentially protected the mice from the disease, even though the cells were outnumbered four to one by their pro-inflammatory counterparts.

"The theory is that if you could restore normal regulatory T cell function, then you could restore their ability to suppress the inflammation process, and prevent this abnormal destruction of your joints," Dr. Abramson says.
Provided by New York University School of Medicine

Tuesday, February 9, 2010

Compugen provides new hope for a universal autoimmune treatment

Compugen discovery of a molecule that can turn off the misbehaving autoimmune part of our immune response while leaving intact the part that fights bacterial and viral disease could be game changer in the field of autoimmune treatments.

The results are in preclinical trials, in the mouse model of multiple sclerosis. We cannot get our hopes up too high. However just the fact that researchers are still generating new and innovative ideas especially one that could be helpful for so many autoimmune diseases does let one contemplate a future without the horror of autoimmune.

Read more here:

Tuesday, January 12, 2010

Hookworms fail to cure asthma. Our hopes dashed.

I hate to report this news. One of the greatest hopes for a 'miracle cure' of asthma, allergy and possibly autoimmune disease has failed in a scientifically controlled clinical trial at the University of Nottingham in England.

As many of you know the group of researchers at Nottingham was the only research group in the world willing to clinically test HUMAN parasitic worms as a way to control or even cure asthma.

The idea of parasitic worms as therapy for our certain autoimmune and allergic diseases was first pioneered by Joel Weinstock then of the University of Iowa.

Weinstock used pig whipworms which could not survive in humans more than a few weeks. He claimed to have success in treating irritable bowel and colitis disorders with these pig parasitic worms. However, the worms being in the wrong host died in a few weeks and whatever benefit they gave to infected patients did not last. Weinstock could not get permission to use human worm parasites.

In the United States, Food and Drug Administration approval is needed for any clinical trial and the FDA insisted on parasites that could not survive in humans and possibly be retransmitted to others.

I like many of you was very disappointed that the US FDA refused requests for trials with human parasites or even with more trials with pig whip worms. We felt that the effects of parasites on calming a hosts immune system held great hope for our diseases. We especially felt that a HUMAN parasite would be much more likely to secret closer analogs to IL-10 and other human immune molecules that reduced inflammation and calmed our over active immune systems. We still held on to our hope that allergy, asthma and autoimmune disease could be helped by these parasites.

In stepped the courageous researchers at the Statens Serum Institut in Copenhagen Denmark who scientifically tested pig whipworms eggs (TSO's--Trichuris suis ovum) for efficacy in treating allergy. In October of last year, our Copenhagen friends released the disappointing results. The pig whipworms failed to help allergy. Perhaps there is still some slight hope that the pig whipworms might help various autoimmune digestive disorders like IBS, IBD, colitis and Crohn's. However their failure to help allergies seems to have thrown cold water even on this dimming hope.

Even after the Danish disappointment, there was still hope for sufferers of allergy, asthma, and autoimmune disease looking for a cure. Perhaps a very different kind of intestinal parasite might help--the hook worms.

Hookworms are in a completely different group of worms--the flat worm family (trematodes) as opposed to the round worm family (nematodes) that the whipworms are in. Perhaps this different family of parasites would work better than the whipworms especially if a HUMAN parasite was used.

Brave researchers at the University of Nottingham decided to give human hookworms a scientifically controlled clinical trial. We held out hope that these researchers would succeed in finally achieving clinical success. Our friends at Nottingham had somehow gained permission to conduct a real scientific trial of actual human parasite. Quick and easy cures with worm parasites still seemed possible.

Sadly our hopes are dashed again. The trial at the University of Nottingham failed to show a clinically significant difference between the group getting the human hookworms and the group who got sham shots of histamines as a control.

The hookworm larva do not enter the body through the mouth as do whipworms. They burrow through the skin which causes a mild rash and some itching. So the control group had to be given something that would duplicate this rash--histamine.

For a clinical trial to be valid neither the doctor nor the patients should know which group of patients received the 'treatment' and which group of patients did not (This process is called doing a "double blind, randomized" procedure.). Those who do not receive treatment must have similar symptoms initially as those that do, hence the histamine.

Sadly the truly infected hook worm group did not show any significantly better asthma control than the sham hook worm infected histamine group. What a huge disappointment!

Read more here:

I have put in bold face type the most significant sentences in the summary below of the University of Nottingham hookworm results for asthma patients:

Clin Exp Allergy. 2009 Dec 16. [Epub ahead of print]
Experimental hookworm infection: a randomized placebo-controlled trial in asthma.
Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, Pritchard DI, Britton JR.

Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
Summary Background Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma.

Objectives To determine the effects of experimental hookworm infection in asthma.

Methods Thirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects.

Results Mean PD(20)AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated.

Conclusions: Experimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.

PMID: 20030661 [PubMed - as supplied by publisher]

Monday, January 4, 2010

Antibiotic Resistance, My Illness (death?)--Big Pharma's role

Over the last six weeks I have been fighting an infection in my nose and sinuses that has defeated antibiotic after antibiotic. I am scared.

I have a hypersensitivity disorder and have been hospitalized twice before with reactions to antibiotics and have had a couple of near death experiences. NOT FUN.

So far the only antibiotic I have tried that actually KILLED the damn bacteria in my nose was a sulfa drug, but after five doses I had a hypersensitivity reaction and was forced to stop.

The quinolone, Avalox, did not kill the bacteria.

Even the highly restricted super drug, Zyvox, has done no more than knock back the infection. The bacteria has not died and I have only two more days left on my two week prescription. Because Zyvox is so dangerours if I continue with it passed two weeks I must have frequent blood tests to monitor for damage to my various blood cells.

Yet as soon as I stop an antibiotic, the infection roars back causing intense pain in my sinuses and nose. It feels like it is eating into the cartilage and bone, just like a nail being pushed in. The pain is almost unbearable, my fever returns.

I need the new antibiotic. But there are no more that I can take. Even if I could it is unlikely that they would work any better than Avelox or Zyvox. There are virtually no new antibiotics in the drug research pipeline. So the rapidly fading almost hopeless place I am in today, you or a loved one could be in tomorrow.

Today I saw immunologist in Carmel Valley north of San Diego who told me he would try a rapid desensitization to sulfa if all else fails. Good news. But still VERY scary, I have at least a one in four chance of dying during the rapid desensitization, as it is very dangerous procedure. The patient is brought to verge of death by increasing doses of the drug, then pulled back repeatedly over a six to eight hour period. And of course, rapid desensitization only works, if I get it in time before the bacteria gets into my blood and goes septicemic. Then I have little chance of survival.

Now I read that this problem with bacteria that will not die, is most likely caused by feeding HEALTHY farm animals and poultry low doses of antibiotics as growth promoters, NOT because the animal is sick. Somehow low dose antibiotics make the HEALTHY animals and birds put on a little more weight a little faster than those not feed low dose antibiotics.

We have known since the mid 1930's that low doses of an antibiotic quickly cause bacteria to be selected which are then resistant to even high doses of the antibiotic.

Shortly after sulfa drugs were discovered the US army tried an experiment on a group of soldiers giving them low doses of sulfa hoping they would stay healthier than other soldiers who were given none. The experiment failed. After several months the low dose soldiers not only got sick as often as non dosed soldiers, but worse for them, the same infections, that were easily cured among the other soldiers, no longer responded to even high doses of sulfa drugs in the low dosed group.

Now we have good evidence that the last of the broad spectrum antibiotics--cephalosporins and quinolones no longer work on many human bacterial infections due to low dose antibiotic use on farms.

Who is prevented the FDA from banning use of low dose antibiotics on HEALTHY farm animals--BIG PHARMA! Why because they sell more antibiotics to farmers for low dose use, then they do to ill Americans. It is all about profit!

We are about to enter a POST antibiotic era in which children die of ear infections and pink eye, most surgeries are not possible, and one in four women die during childbirth.

Is that what we want for our children's future? Fight back against BIG PHARMA. Call your congressman today. Call a radio talk show host and ask them to support the ban.

Read more here:

Pressure rises to stop antibiotics in agriculture
By MARGIE MASON AND MARTHA MENDOZA, Associated Press Writers Margie Mason And Martha Mendoza, Associated Press Writers
Tue Dec 29, 7:49 am ET

FRANKENSTEIN, Mo. – The mystery started the day farmer Russ Kremer got between a jealous boar and a sow in heat.

The boar gored Kremer in the knee with a razor-sharp tusk. The burly pig farmer shrugged it off, figuring: "You pour the blood out of your boot and go on."

But Kremer's red-hot leg ballooned to double its size. A strep infection spread, threatening his life and baffling doctors. Two months of multiple antibiotics did virtually nothing.

The answer was flowing in the veins of the boar. The animal had been fed low doses of penicillin, spawning a strain of strep that was resistant to other antibiotics. That drug-resistant germ passed to Kremer.

Like Kremer, more and more Americans — many of them living far from barns and pastures — are at risk from the widespread practice of feeding livestock antibiotics. These animals grow faster, but they can also develop drug-resistant infections that are passed on to people. The issue is now gaining attention because of interest from a new White House administration and a flurry of new research tying antibiotic use in animals to drug resistance in people.

Researchers say the overuse of antibiotics in humans and animals has led to a plague of drug-resistant infections that killed more than 65,000 people in the U.S. last year — more than prostate and breast cancer combined. And in a nation that used about 35 million pounds of antibiotics last year, 70 percent of the drugs went to pigs, chickens and cows. Worldwide, it's 50 percent.

"This is a living breathing problem, it's the big bad wolf and it's knocking at our door," said Dr. Vance Fowler, an infectious disease specialist at Duke University. "It's here. It's arrived."

The rise in the use of antibiotics is part of a growing problem of soaring drug resistance worldwide, The Associated Press found in a six-month look at the issue. As a result, killer diseases like malaria, tuberculosis and staph are resurging in new and more deadly forms.

In response, the pressure against the use of antibiotics in agriculture is rising. The World Health Organization concluded this year that surging antibiotic resistance is one of the leading threats to human health, and the White House last month said the problem is "urgent."

"If we're not careful with antibiotics and the programs to administer them, we're going to be in a post antibiotic era," said Dr. Thomas Frieden, who was tapped to lead the Centers for Disease Control and Prevention this year.

Also this year, the three federal agencies tasked with protecting public health — the Food and Drug Administration, CDC and U.S. Department of Agriculture — declared drug-resistant diseases stemming from antibiotic use in animals a "serious emerging concern." And FDA deputy commissioner Dr. Joshua Sharfstein told Congress this summer that farmers need to stop feeding antibiotics to healthy farm animals.

Farm groups and pharmaceutical companies argue that drugs keep animals healthy and meat costs low, and have defeated a series of proposed limits on their use.


America's farmers give their pigs, cows and chickens about 8 percent more antibiotics each year, usually to heal lung, skin or blood infections. However, 13 percent of the antibiotics administered on farms last year were fed to healthy animals to make them grow faster. Antibiotics also save as much as 30 percent in feed costs among young swine, although the savings fade as pigs get older, according to a new USDA study.

However, these animals can develop germs that are immune to the antibiotics. The germs then rub into scratches on farmworkers' arms, causing oozing infections. They blow into neighboring communities in dust clouds, run off into lakes and rivers during heavy rains, and are sliced into roasts, chops and hocks and sent to our dinner tables.

"Antibiotic-resistant microorganisms generated in the guts of pigs in the Iowa countryside don't stay on the farm," said Union of Concerned Scientists Food and Environment director Margaret Mellon.

More than 20 percent of all human cases of a deadly drug-resistant staph infection in the Netherlands could be traced to an animal strain, according to a study published online in a CDC journal. Federal food safety studies routinely find drug resistant bacteria in beef, chicken and pork sold in supermarkets, and 20 percent of people who get salmonella have a drug resistant strain, according to the CDC.

Here's how it happens: In the early '90s, farmers in several countries, including the U.S., started feeding animals fluoroquinolones, a family of antibiotics that includes drugs such as ciprofloxacin. In the following years, the once powerful antibiotic Cipro stopped working 80 percent of the time on some of the deadliest human infections it used to wipe out. Twelve years later, the New England Journal of Medicine published a study linking people infected with a Cipro-resistant bacteria to pork they had eaten.

Johns Hopkins University health sciences professor Ellen Silbergeld, who has reviewed every major study on this issue, said there's no doubt drug use in farm animals is a "major driver of antimicrobial resistance worldwide."

"We have data to show it's in wastewaters and it goes to aquaculture and it goes here and there," agreed Dr. Stuart Levy, an expert on antibiotic resistance at Tufts University in Boston. "Antibiotic use in animals impacts everything."


Farmer Craig Rowles remains unconvinced.

It's afternoon in one of his many rural Iowa pig barns, roaring with snorting and squealing pigs. Some snooze in corners, while others hustle toward their troughs, their slop laced with a steady supply of antibiotics.

"If there was some sort of crossover between the use of the antibiotics in animals and the antibiotics in humans, if there was in fact a real issue there, wouldn't you think we would have seen it?" said Rowles, also a veterinarian who sells 150,000 hogs a year. "That's what the science says to me."

The modular modern barn, home to 1,000 pigs, is a hygienic place. Manure plops through slatted floorboards; an invisible funk steams back up. Rowles dons a sanitary white paper jumpsuit and slips plastic booties over his shoes; he's anxious that his 100-pound pigs aren't exposed to outside germs. A few sick swine are isolated, corralled in a pen near the entrance.

Antibiotics are a crucial part of Rowles' business, speeding growth and warding off disease.

"Now the public doesn't see that," he said. "They're only concerned about resistance, and they don't care about economics because, 'As long as I can buy a pork chop for a buck 69 a pound, I really don't care.' But we live in a world where you have to consider economics in the decision-making process of what we do."

Rowles gives his pigs virginiamycin, which has been used in livestock for decades and is not absorbed by the gut. He withdraws the drug three weeks before his hogs are sent for slaughter. He also monitors his herd for signs of drug resistance to ensure they are getting the most effective doses.

"The one thing that the American public wants to know is: Is the product that I'm getting, is it safe to eat?" said Rowles, whose home freezer is full of his pork. "I'm telling you that the product that we produce today is the safest, most wholesome product that you could possibly get."


Some U.S. lawmakers are fighting for a new law that would ban farmers like Rowles from feeding antibiotics to their animals unless they are sick.

"If you mixed an antibiotic in your child's cereal, people would think you're crazy," said Rep. Louise M. Slaughter, D-N.Y.

Renewed pressure is on from Capitol Hill from Slaughter's bill and new rules discussed in regulatory agencies. There is also pressure from trade issues: The European Union and other developed countries have adopted strong limits against antibiotics. Russia recently banned pork imports from two U.S. plants after detecting levels of tetracycline that the USDA said met American standards.

Farmers and drugmakers are battling back. Pharmaceutical companies have spent $135 million lobbying so far this year, and agribusiness companies another $70 million, on a handful of issues including fighting the proposed new limits. Opponents, many from farm states, say Slaughter's law is misguided.

"Chaos will ensue," said Kansas Republican Congressman Jerry Moran. "The cultivation of crops and the production of food animals is an immensely complex endeavor involving a vast range of processes. We raise a multitude of crops and livestock in numerous regions, using various production methods. Imagine if the government is allowed to dictate how all of that is done."

He's backed by an array of powerful interests, including the American Farm Bureau, the National Pork Producers Council, Eli Lilly & Co., Bayer AG, Pfizer Inc., Schering-Plough Corp., Dow AgroSciences and Monsanto Company, who have repeatedly defeated similar legislation.

The FDA says without new laws its options are limited. The agency approved antibiotic use in animals in 1951, before concerns about drug resistance were recognized. The only way to withdraw that approval is through a drug-by-drug process that can take years of study, review and comment.

In 1977 the agency proposed a ban on penicillin and tetracycline in animal feed, but it was defeated after criticism from interest groups.

There has been one ban: In 2000, for the first time, the FDA ordered the poultry medication Baytril off the market. Five years later, after a series of failed appeals, poultry farmers stopped using the drug.

In 2008 the FDA issued its second limit on an antibiotic used in cows, pigs and chickens, citing "the importance of cephalosporin drugs for treating disease in humans." But the Bush Administration — in an FDA note in the federal register — reversed that decision five days before it was going to take effect after receiving several hundred letters from drug companies and farm animal trade groups.

Laura Rogers, who directs the Pew Charitable Trusts Campaign on Human Health and Industrial Farming in Washington D.C., says the federal government, from Congress to the administration, has failed to protect the public.

"Because of poor regulations and oversight of drug use in industrial farm animals, consumers in the U.S. do not know what their food is treated with, or how often," she said. "Nor is there a system in place to test meat for dangerous antibiotic resistant bacteria."


Back in Missouri, farmer Kremer finally found an antibiotic that worked on his leg. After being released from the hospital, Kremer tested his pigs. The results showed they were resistant to all the same drugs he was.

Kremer tossed his hypodermic needles, sacked his buckets of antibiotic-laced feed, slaughtered his herd and started anew.

"I was wearing a syringe, like a holster, like a gun, because my pigs were all sick," he recalled. "I was really getting so sick and aggravated at what I was doing. I said, 'This isn't working.'"

Today, when Kremer steps out of his dusty and dented pickup truck and walks toward the open-air barn in the foothills of the Ozark Mountains, the animals come running. They snort and root at his knee-high gum boots. There are no gates corralling the 180 pigs in this barn. He points to a mound of composting manure.

"There's no antibiotics in there," he says proudly.

Kremer sells about 1,200 pigs annually. And a year after "kicking the habit," he says he saved about $16,000 in vet bills, vaccinations and antibiotics.

"I don't know why it took me that long to wake up to the fact that what we were doing, it was not the right thing to do and that there were alternatives," says Kremer, stooping to scratch a pig behind the ear. "We were just basically killing ourselves and society by doing this."


Martha Mendoza is an AP national writer based in Mexico City. Margie Mason is an AP medical writer who reported from Missouri and Iowa while on a fellowship from The Nieman Foundation at Harvard University.