Clinical Trials Underway Using Worms to Treat Auto-Immune Diseases Like Crohn's

from wsj.com

Some bugs are good for our health, and a pig parasite called the whipworm appears to be one of them.

Whipworm eggs have been found in human studies to reduce symptoms in a host of diseases that affect the immune system. Researchers at several universities have shown promising results in small numbers of patients with multiple sclerosis, Crohn's disease and ulcerative colitis. Biotechnology companies are conducting large clinical trials of the treatment. Other studies targeting rheumatoid arthritis, autism and some allergies are expected to begin this year.

Scientists have been trying to figure out why diseases that affect the immune system have increased dramatically over the past several decades in much of the developed world. For example, the incidence of asthma in U.S. children under 17 was up 28% in 2009 from 1999, according to government data.

The whipworm treatment was born from a theory known as the hygiene hypothesis, which essentially says our environment has become too clean. Humans aren't exposed to microorganisms in the environment as much as they used to be, when more people farmed or lived closely with animals.

While many diseases have diminished thanks to improved hygiene and medicine, people aren't exposed to bacteria that helped regulate the immune system, the theory goes. This lack of exposure may, in part, be responsible for the increase in diseases in which the body's immune system goes awry.

Based on this hygiene hypothesis, researchers at the University of Iowa wanted to find a safe parasite—one that wasn't known to cause infection or illness in humans—for therapeutic purposes. This type of treatment is known as helminthic treatment, or more specifically TSO, from the Latin name for whipworm eggs: Trichuris Suis Ova.

many autoimmune diseases, immune cells known as T1 cell cytokines proliferate and fight against the body's cells, the way they do when the body detects foreign invaders.

A Beneficial Bug?

Clinical trials using whipworm therapy have been run or are planned for the following conditions:

• Crohn's disease
• Ulcerative colitis
• Multiple sclerosis

• Rheumatoid arthritis
• Psoriatic arthritis
• Autism

• Tree nut allergy
• Seasonal allergy (hay fever)

Source: Coronado Biosciences

Patients and study participants consume microscopic whipworm eggs, above left, which hatch into worms, right, in the intestines. The worms appear to spur a beneficial immune-system reaction.

The introduction of the whipworm appears to spur the body to produce more of a different type of helpful immune cell—T2 helper cytokines—as a defense against the worms. This separate immune response appears to help counter the inflammatory response from diseases, say researchers.

This approach differs from many available treatments on the market for inflammatory diseases. If these drugs, which tend to suppress the immune system, are given in doses that are too high, the immune system can be compromised, says Robert Summers, a professor in gastroenterology and hepatology at the University of Iowa who helped run the trials.

TSO treatment is likely to be much less hazardous because it doesn't directly attack the body's immune system, says Dr. Summers.

When it comes to using bugs as treatment, one key, of course, is finding ones that won't sicken people.

Whipworm from pigs appeared to be a good candidate because they don't naturally infect humans and can't reproduce in them. Once the eggs are ingested, they pass through the stomach to the intestine. There, the worms hatch and latch on, and apparently prompt the modulating effect in the immune system. After about two weeks, they die and are absorbed or excreted.

Dr. Summers and his colleagues demonstrated encouraging findings in two studies published in 2005. One examined 29 patients with Crohn's disease and found that after six months, 21 were considered remitted. (There wasn't a control group for comparison.) The other was study of 54 patients with ulcerative colitis. Patients who received TSO treatment improved significantly more than those who got placebo.

Another area of interest for TSO researchers is in multiple sclerosis, with two small studies published last year. One of these, published in the Multiple Sclerosis Journal, showed brain lesions decreased in four of five patients three months into treatment, and rebounded two months after it ended.

Some researchers say the therapy could hold promise for autism as well.

Eric Hollander, director of the Autism and Obsessive-Compulsive Spectrum Program at Montefiore Medical Center and Albert Einstein School of Medicine in the Bronx, N.Y., expects to begin recruiting for a human trial in adults with autism by the end of March.

"People are just beginning to think about modifying the immune inflammatory response to see if it has some sort of effect on behavioral symptoms," says Dr. Hollander.

In 2005, Stewart Johnson, a portfolio manager at an insurance company in New York, and his wife were at their "absolute limit" with their then 14-year-old autistic son. Mr. Johnson says he exhibited extremely disruptive behaviors, and agitation. The Johnsons were close to putting their son in a residential facility.

Around this time their son made his yearly trip to summer camp—always a difficult time.

But one day, says Mr. Johnson, a camp counselor called, saying his son was calm and behaving better than he had ever seen. The night after Mr. Johnson picked up his son—finding he was indeed well-behaved—he saw his son's legs were covered with many bites from chiggers, the larvae of mites. After about 10 days, the disruptive behaviors returned. "I said, 'this can't be coincidence,'" says Mr. Johnson.

He started doing research, heard theories that the immune system may play a role in autism, and came across the work on whipworm eggs and Crohn's disease. He was able to obtain a supply to test on his son, though first he took the ova himself to make sure they were safe. The eggs, which aren't yet available in the U.S., cost €300 ($396) for a two-week vial, Mr. Johnson says.

After a reduced dosage of the invisible, tasteless eggs failed to help, Mr. Johnson consulted with the supplier, OvaMed GmbH, of Barsbüttel, Germany, and bumped up the dosage. In about 10 weeks, the disruptive behaviors ceased.

The younger Mr. Johnson, who declined to comment, lives at home and has been taking the eggs ever since. The worst symptoms don't return so long as he stays on the treatment, Mr. Johnson says.

Write to Shirley S. Wang at shirley.wang@wsj.com

The Surgery that Brought Back Adele's Voice

from scientificamerican.com

You would never have known it from her performance at the Grammy Awards ceremony on Sunday night, but the British singer Adele was not even allowed to speak for most of November and December. She had just undergone laser surgery to remove a polyp from her vocal folds, a small growth that forced her to cancel a U.S. tour and threatened to damage her sultry voice permanently. It was an extreme form of an injury that anyone can get simply by yelling too much.

The problems began last May, Adele wrote in her blog: “I made a Skype call in the morning on the day of the show and during it my voice suddenly switched off like a light! It was literally as if someone pulled a curtain over my throat.” At a show soon afterward, Adele described feeling a “ripping” sensation in her throat, which her doctors diagnosed as a hemorrhage. They ordered her to rest her voice and reschedule several performances.

A vocal cord hemorrhage such as Adele’s happens because of the physical stresses of singing or speaking. When Adele first began noticing problems with her voice, she said she had never sung so much in her life. When vocal cords areoverworked or injured, they can bruise just like other body parts—in the larynx, blood escapes the tiny blood vessels and floods the vibrating flaps that allow a person to talk or sing. The bleeding and subsequent swelling can stiffen the vocal cords and interfere with their undulations, leading to hoarseness, or in some cases (such as Adele’s) the inability to speak at all. Many people experience minor vocal cord damage after yelling at a sporting event or noisy bar. In most cases, these can be treated by simply resting the voice.

Read more at scientificamerican.com

Alzheimer's Families Clamor for Drug

In the wake of research suggesting a skin-cancer drug may have benefits in treating Alzheimer's disease, physicians and advocacy groups are getting a flurry of calls from patients seeking to use the drug off-label.

The clamor underscores how urgently patients want solutions to the rising tide of Alzheimer's. But experts caution that more research is needed to determine whether the drug, bexarotene, is effective in humans at all, not to mention what the dosage should be

The study, published Thursday in the journal Science, was conducted in mice, and the road to an effective Alzheimer's treatment is littered with failures that looked promising early on in animals.

"The Alzheimer's community is very desperate for anything that shows any sign of hope or promise," said Eric Hall, chief executive of the Alzheimer's Foundation of America, a New York-based advocacy organization that started to field calls from consumers as soon as the paper was published.

While Mr. Hall said he was "cautiously optimistic" about the drug, which appears to clear a sticky substance called amyloid from the brains of Alzheimer's mice, "I don't think people should be taking this in their own hands or running to it," he said.

Read the story at WSJ.com

The Drug That Helps Phil's Game

When Phil Mickelson beat Tiger Woods at Pebble Beach this weekend he said, "I believe now more so that what I am doing is correct and that I'm able to play some of my best golf."  Reading between the lines of his comments, we see a rousing endorsement for the biological drug Enbrel, which Mickelson publically promoted shortly after announcing his 2010 diagnosis with psoriatic arthritis--an auto-immune disease that attacks the joints and can rob people of the ability to even button their shirts let alone beat Tiger Woods.

The difference between TNF-alpha inhibitors and steroids like Prednisone (the previous standard treatment for such auto-immune disorders) is like the difference between laser guided missiles and the fire-bombs used to flatten entire cities during WW II.

That Mickelson is able to play elite golf with his diagnosis is nothing short of miraculous.  While it's always desirable to try gentler remedies, patients and doctors have noted a major game-change with the Enbrel class of drugs known as Tumor Necrosis Factor-alpha Antagonists, which work by tamping down the immune protein (TNF-alpha) that runs wild, attacking healthy tissues in certain autoimmune diseases including Mickelson's arthritis, and the Inflammatory Bowel Diseases Crohn's and Ulcerative Colitis.

The difference between TNF-alpha inhibitors and steroids like Prednisone (the previous standard treatment for such auto-immune disorders) is like the difference between laser guided missiles and the fire-bombs used to flatten entire cities during WW II. The new biological agents effictively minimize symptoms while allowing patients to lead relatively normal lives by suppressing a tiny portion of the immune system.  

Recently, the users of these drugs had additional good news, along with Mickelson's seemingly happy results. While TNF-alpha inhibitors are a huge biopharm success story (Enbrel's sister drug Humira is poised to become the nation's top selling drug this year) they come with a host of frightening warnings about dangerous side-effects, most all of which have to do with the immune system being compromised--there's a generally elevated risk of infections spiriling out of control and a minutely elevated risk of developing a deadly cancer.  

But a recent large-scale study of 16,000 people taking the drugs published in the Journal of the American Medical Association found no elevated risk of infection associated with TNF-alpha inhibitors. That should come as no surprise to people using the drugs successfully, but a huge relief to those considering starting them.

Cost is the other major issue for TNF-alpha inhibitors, which come with a hefty co-pay and are unaffordable for all but the wealthiest people without insurance. But even this downside received a possible solution last week when the FDA created the first shortcut to the U.S. market for "biosimilar" drugs—cheaper (rather like generic) versions of expensive and complex medicines like Enbrel made from biological matter. Drug companies will no doubt extend their patents to counter cheaper copycats, but it's at least progress in reducing the costs.

All in all it's been a good year for people taking these brave new drugs.

Update on Friday, June 8, 2012 at 3:52PM by Kathy

from WSJ.com

It’s not always fun being compared to the competition. But Embrel's main competition, Humira is under attack for being on top.

But, Roche Holdings AG took the chance with a head-to-head study it financed pitting its rheumatoid arthritis treatment Actemra against the market-leader Humira, Abbott Laboratories’ blockbuster.

Actemra fared better at reducing arthritis symptoms—swollen, painful joints—according to the study results, presented Friday morning at a European arthritis conference. Actemra is made by Roche’s Genentech unit.

Roche has been positioning its drug as a first pick for doctors and patients in the increasingly crowded rheumatoid arthritis market, long dominated by Humira, which is expected to have $9 billion in sales this year. At least seven other drug makers market are developing biologic arthritis treatments, according to a report from research firm Datamonitor. Pfizer and a partnership between Lilly and Incyte have pills in development, an easier alternative to the injectable treatments now on the market.

Humira’s patent expires at the end of 2016, and at least one other company is runninga clinical trial to test the safety of its own “biosimilar” version of the treatment.

The Roche study, along with other new data including a Bristol-Myers Squibb Co. finding that its arthritis treatment Orencia is comparable to Humira, “raise the prospect of slowing Humira growth,” wrote Credit Suisse stock analyst Catherine Arnold in a note earlier this week, when abstracts of the studies were released. Still, analysts said it was unlikely recent developments would hurt Humira sales soon.

Abbott said the trial used a low dose of Humira, a design element that may have favored Actemra. Also, it evaluated only symptoms of arthritis, and not the physical evidence of disease activity, which can be measured by x-rays, said Elizabeth Hoff, an Abbott spokeswoman.

“Abbott is confident in our ability to continue to grow Humira based on its long term proven efficacy in a broad patient population,” Ms. Hoff said.

The Roche study compared 163 Actemra patients to 162 similar Humira patients over a 24 week period, but was limited to patients taking only a biologic treatment for arthritis. Most arthritis patients receive biologics—including Actemra and Humira—along with other drugs such as methotrexate, because their results are thought to improve in combination.

But, not all patients can tolerate methotrexate, a potent chemotherapy agent with considerable side effects, such as fatigue and increased risk of infections. Roche estimates as many as one-third of rheumatoid arthritis patients don’t do well on that drug. The trial didn’t include any finding the relative effectiveness of Actemra and Humira in combination with other drugs.

Roche hopes doctors will steer more arthritis patients to Actemra if they struggle with methotrexate, rather than advising them to use Humira alone. “These data will be informative to physicians,” Sunil Agarwal, head of Roche’s immunology and infectious diseases section, tells the Health Blog. The head-to-head comparison is the first trial designed to show whether one biologic arthritis treatment is better than another, Agarwal says.

Right now, Actemra is used as a back-up drug for patients who don’t respond to so-called first-line therapies, including Humira. Roche asked the FDA in December to broaden the approval to patients who haven’t yet tried other treatments.

Breast Outrage

While Komen v. Planned Parenthood has us all fired up about access to breast cancer screening let's talk about the pathetic state of the actual screening technology.  Why is that in the 50 years mammography has been in use there's been no progress in improving the experience of having a mammogram and relatively little progress in improving the accuracy of detection? Perhaps more importantly, why is it that new and better technologies are ignored or left underfunded?

Molecular Breast Imaging or MBI (right) vs standard mammography (left): MBI doesn't require compression and is 3 times more accurate than regular mammography. Why has this new breast screening technology been buried?

Mammography is a relatively primitive technology. It is the only radiological study regulated by federal law, which requires the equivalent of a 40 pound car battery to be lowered onto the breast during the test. It is the most difficult radiological test to read, partly because breasts vary so greatly from woman to woman. Looking for a tumor is truly like searching for a needle with a blindfold in a haystack.

Molecular Breast Imaging is pain free (requiring 2/3 of the compression of standard mammograms) and significantly increases tumor detection accuracy (by as much as 300%.)

The so-called "revolution" of digital mammography does absoutely zero for eliminating the pain of the experience, and while it does increase the accuracy of diagnosis for women with low breast density, digital mammorgraphy only moderately improves accuracy (with a 60% detection rate) in detecting tumors in women with highly dense breasts (a full 2/3 of women in their forties) who are at a higher risk of developing aggressive breast tumors. The federal government invested $4 billion converting to digital mammography over the past decade, an incredible boon to digital mammogram manufacturers, but an exceedingly small advance for womens health. 

it's incredible when you compare the advances made in, say, smartphone technology versus mammography. What is even more mind-blowing is the fact that there is a better breast cancer screening technology --Molecular Breast Imaging (MBI) using gamma rays, developed at the Mayo Clinic (spurred by Dr. Deborah Rhodes.) MBI is pain free (requiring 2/3 of the compression of standard mammograms) and significantly increases tumor detection accuracy (by as much as 300%.) This technology has met resistance in the radiological community, as Dr. Rhodes says, "The forces in breast imaging prefer the status quo.." Learn about this new technology by watching Dr. Rhodes TED talk below. And ponder with me why it is that we can't improve the experience and accuracy of breast cancer screening?