Crohn's caused by showers and rivers?

New research from Lancaster University has found the MAP pathogen associated with Crohn's Disease to be present in 10% of domestic showers sampled and in the spray from a Welsh river. It is suggested that these may be mechanisms by which people can be infected, and that this may be a trigger for Crohn's.

It has long been suspected that the consumption of milk may be the route for MAP to enter the human body, but this appears to be the first research into infection through inhalation. However, it should be noted that it has yet to be proven that MAP is the cause of Crohn's. Even if MAP is present in most people in Crohn's it does not necessarily mean that it was the cause rather than a result of the condition.

Full details of this research can be read for free in the open access journal Pathogens.

Worms trial terminated

A disappointing report from Medpage Today indicates that a German trial of whipworm for the control of Crohn's Disease has been cancelled due to poor results. Whilst there were no safety concerns from the trial the hoped for response to the treatment had not occurred.

Although there is plenty of anecdotal evidence of the effectiveness of helminths, to date I know of no full-scale clinical trials which have proven successful. I hope the failure of this trial will prompt researchers to investigate further and propose further avenues of to explore in this promising area.

Crohn's vaccine

Mycobacterium avium subspecies paratuberculosis (MAP) has been a contender as a cause of Crohn's for a while, but nothing conclusive has been determined. It causes the Crohn's-like Johne’s disease in cattle, and people with Crohn's are significantly more likely to have MAP in their intestines than non-sufferers. The theory is that susceptible people who drink MAP-contaminated milk will may develop Crohn's. Pasteurisation of milk does not eliminate MAP, but ultra-heat treatment, as used in long-life milks, does.

The Western Farm Press has an interview with veterinary professor William Davis which outlines why he believes the MAP link to Crohn's should be investigated further.

"We know the incidence of Johne’s is on the rise, as is the incidence of Crohn’s,” said Davis, whose research has included collaboration with physicians and immunologists. "The problem is too important and the theory is sufficiently plausible that we need to be taking a closer look. More research is necessary to resolve exactly what the link is.”

He also notes that preliminary work has found that his vaccine against MAP in cattle has seemed effective. If it is successful then this may eliminate MAP entering the human food chain, and possibly reducing the incidence of Crohn's.

Note, however, that antibiotics to combat MAP have thus far been ineffective against Crohn's, and the MAP link is far from proven.

Vitamin D may reduce risk of developing Crohn's

Two years after two previous reports on the role vitamin D may play in the development of Crohn's Disease, Medscape has noted the results of a new study. It found that women deficient in vitamin D were far more likely to develop Crohn's. The researchers went on to suggest that this would make vitamin D supplements a potential area of interest in the treatment of active Crohn's or the maintenance of remission.

New Scientist calls for worm investigation

An editorial in the latest New Scientist, Let them eat worms, calls for a relaxation of regulations so that full-scale clinical trials into the use of parasitic worms called helminths can be undertaken. A story in issue 2824, Citizen scientists eat worms to treat disorders (subscription required) [titled "One sugar or two with your parasites?" in the print edition], further explains why helminthic therapy is so promising.

Small trials run in the past ten years, including those by Joel Weinstock of Tufts University, and John Crease of Townsville Hospital, have shown promising results. The expansion to larger trials has not occurred because of the safety issues involved in infecting large groups of volunteers with living organisms, with the potential for severe illness to result. Some researchers feel that the mechanism by which helminths subdue the immune system should be determined and replicated with medication, rather than introducing worms into the patients.

The usage of worms to treat Crohn's disease has been a promising avenue of investigation for a number of years now, but not much progress has been made. Anecdotally, worms seem to be more successful and produce fewer side-effects than many of the current medicines. However, people should not have to experiment on themselves to find if worm therapy is their best course of action. Full-scale clinical trials are needed, and proper scientific analysis to work out if it should be added to the mainstream options available for the treatment of Crohn's.

Infliximab effective after surgery

Research published in Clinical Gastroenterology and Hepatology shows the continuation of infliximab after surgery is effective and useful, even at a low dose.

Patients were given infliximab for three years after surgery, and those with no symptoms then ceased the medication. 83% of those then showed clinical symptoms after a few months, and they were put back onto a low dose of infliximab. This controlled the disease in all patients.

Whilst it's disappointing that most patients were unable to remain in remission without medication, the success of a lower than standard dosage is good news.

Vitamin D to combat Crohn's

Two new studies have pointed to Vitamin D having a role in fighting Crohn's. Scientists believe that the boost to the immune system provided by Vitamin D could benefit Crohn's sufferers, and perhaps ensuring adequate Vitamin D levels could prevent Crohn's from occurring.

As noted in Science Daily:

Dr. White and his team found that Vitamin D acts directly on the beta defensin 2 gene, which encodes an antimicrobial peptide, and the NOD2 gene that alerts cells to the presence of invading microbes. Both Beta-defensin and NOD2 have been linked to Crohn's disease. If NOD2 is deficient or defective, it cannot combat invaders in the intestinal tract.

The Telegraph states:

“Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn’t realise is how crucial vitamin D is for actually activating the immune system – which we know now, ” said the researchers.

It's interesting that these different mechanisms for Vitamin D to enhance the immune systems have been reported on almost simultaneously. Although their link to Crohn's is speculative, it opens further avenues for research. Who wouldn't hope for a cod liver oil tablet cure?

Genes causing defective gut lining

The BBC reports that research comparing the genes of thousands of people with or without ulcerative colitis has found four genes of interest. They affect the lining of the intestine, and in those with ulcerative colitis the lining may be letting excessive bacteria through.

Researcher Dr Miles Parkes, Consultant Gastroenterologist at Addenbrooke's Hospital, Cambridge, said: "We have long suspected that genetic defects in the epithelial barrier are important in ulcerative colitis.

"This large scale genetic study provides the first robust genetic evidence that this is the case."

More detailed information about this research is available from the Wellcome Trust.

With the ever increasing knowledge of genetic factors influencing inflammatory bowel disorders it's only a matter of time before more effective and better targeted treatments can be found.

Ineffective interleukin-10?

The Atlanta Journal-Constitution reports that a small study of children with severe colitis has found a genetic mutation that reduced the effectiveness of interleukin-10 in their immune systems. Researchers are now considering whether a subset of adult Crohn's cases have a similar cause. If so, then a more direct treatment could be found.

One child in the study was completely cured by a bone marrow transplant. Although such transplants have been used for severe Crohn's cases, they are highly risky. This research should assist in determining the efficacy of such a treatment.

Interleukins have been implicated in Crohn's in the past, but this is the first study to target IL-10 in particular. It has been suggested that Crohn's is a blanket term for a variety of IBD conditions of various causes, and this research is another indication that this may be true.

Weak immune response blamed

In the long-running debate over whether Crohn's is caused by over-active or under-active immune systems the New Scientist reports on research that tips it in favour of the under-active hypothesis.

Segal and his colleagues got their first clue when they noticed a weaker immune response in people with Crohn's than in healthy people after both groups were injected with heat-killed Escherichia coli. The team reasoned that this lukewarm response might allow an infection to build up and eventually trigger a debilitating secondary immune response, resulting in Crohn's.

...

The team concluded that ineffectual rallying of immune cells in people with defective macrophages is what allows intestinal bacteria to run amok in the early stages of an infection, setting in motion the series of events that leads to Crohn's disease.

The full research published in the The Journal of Experimental Medicine contains the juicy details in addition to good background information on the current status of Crohn's research. Although they don't specifically mention new treatments resulting from this discovery, it seems likely to open new avenues for scientists to explore.

Gene implicated in faulty immune response

Research from McGill University Health Centre has shown a link between a gene mutation present in 25% of Crohn's patients and a lack of immune response to mycobacteria. When this connection is fully understood it may lead to new therapies for Crohn's targeting the NOD2 gene involved.

As explained by the lead researcher, Dr. Marcel Behr:

"Now that we have a better understanding of the normal role of NOD2, we think that a mutation in this gene prevents mycobacteria from being properly recognized by the immune system," explained Dr. Behr. "If mycobacteria are not recognized, the body cannot effectively fight them off and then becomes persistently infected."

The full article is published in the Journal of Experimental Medicine (full article requires subscription).

Nutrition therapy helps most children

UPI summarises a report in the Journal of Pediatric Gastroenterology and Nutrition that states that 60% of children with Crohn's will enter remission if they take a special nutrient mixture. This is as effective as steroids, and much preferable to the side-effects of long-term steroid use. However, it's a big commitment for the children:

Maintaining remission may require receiving 25 percent-50 percent of caloric intake by nutrition therapy -- sometimes for years, Shamir says. Children experiencing the treatment need the support of physicians, dietitians, psychologists and their families, the study says.

Although the reason that this works is not known, the fact that it works well and without side-effects makes it a great choice for children. Its benefits for adults are not mentioned, but one hopes that those studies are in process.

Early results for Crohn's cure

The Guardian reports that initial results from the first ever controlled stem cell trial (blogged previously in 2007, before the trial started) are very encouraging, with the leader of the trial expressing an expectation that half of the subjects will be cured.

Given the potentially fatal side-effects of the treatment it will only be an option for those most severely afflicted:

The stem cell treatment, which takes two years, is very painful for patients, and involves risks including bleeding, infection and a 1-2% chance of death. The stem cell transplantation is used to kill off the patient's old bone marrow that produces the harmful cells which cause the Crohn's and generate new healthy cells.

In reality it's far too early to consider a cure for Crohn's, especially as we still do not know the cause of the disease. Only long-term follow-ups of the stem cell trial participants will indicate its success as a cure. However, given the dangers in this treatment it is still not an option for the majority of sufferers, and so the research continues.

Infliximab and Azathioprine combo works best

In October last year I noted a report that Infliximab worked better than Azathioprine, and their combination worked better than Azathioprine alone. A new report in Forbes about a larger, lengthier study confirms the earlier report, and finds that the combination of drugs is significantly more effective than either alone.

After 50 weeks, 72.2 percent of patients who'd received the infliximab/azathioprine drug combination were in steroid-free remission, compared to 60.8 percent who'd received infliximab alone and 54.7 percent who had taken azathioprine alone, according to a Digestive Disease Week news release.

Of additional interest is that the subjects of the study commenced their medication regimes earlier in the disease's progression than is usual. The success of this treatment may influence when these drugs are used in future.

Would you like some worms with that?

Bearing in mind that "the plural of anecdote is not data", CBS has a report on a couple of Crohn's patients who attribute their reduced symptoms to self-administered hookworms. As it is not an approved therapy in the US it is quite an adventure to obtain.

Aglietti, who calls himself a gastrointestinal ecologist, takes clients across the border where he gives them a band aid to put on their arm.

On the gauze on the band aid, there is hookworm larvae.

Scots said he experienced some itching where the band aid was, which he understood, was the larvae making their way into the blood stream.

What happens next is the hookworms then travel from the blood stream into the lungs, where once there, causes the patient to naturally cough. Patients then cough the microscopic helminthes up into the throat, then swallow them, and this is how hookworms get to the intestines, where they latch on, and they begin to mature.

There are few ongoing studies into the use of hookworms to treat Crohn's. If it was shown to be successful then scientists would try to isolate the mechanism of its action. This should lead to a safer treatment using controlled medications, rather than live animals. I'm sure that would be much easier to swallow for many people.

More Crohn's genes found

There hasn't been much Crohn's news for the past few months, but I expect it to pick up around conference time. In the meantime The Children’s Hospital of Philadelphia has released information about a new technique for finding genes associated with a given disease. The researchers have tested this in the area of Crohn's and already found new genes related to the disease.

In a complex disorder such as Crohn's disease, many different genes interact to cause the illness. Research over the past few years have identified many of the genes with the strongest effects, but many other genes with important roles may produce weaker or ambiguous signals in the large-scale studies, and go overlooked.

For children and adults with Crohn's disease, who suffer the debilitating effects of chronic gastrointestinal inflammation, the emerging gene data may open the doors to more effective treatments. "Blocking cell receptors at some points on a biological pathway may produce clinical improvements, but with side effects to the immune system," said Baldassano. "If we can block other molecules further downstream on a pathway, we may achieve better treatments that may be more specific to an individual patient, with fewer side effects."

The full research is available in The American Society of Human Genetics (pay to view).

Monoclonal Antibody Decoder

I've created a simple online tool, the MAB Decoder (see the top right of this page) to decode the generic name of any monoclonal antibody. For example, type in the common Crohn's medication infliximab to find from which animal species it is derived, and what part of the body it acts upon. This can be important because human-sourced antibodies are often better tolerated than those from other animals, which may influence your choice of medications. New monoclonal antibodies are being generated all the time, and often you'll see some new ones mentioned in passing. With this tool you simply enter their names to be able to learn more about them.

The MAB Decoder works with generic rather than brand names. Humira, for example, should be entered as adalimumab (the generic name of monoclonal antibodies always end in -mab). Incidentally, it is useful to be familiar with generic names because brand names may vary from country to country.

You can read more about monoclonal antibody naming at Wikipedia.

Although I created this tool to investigate Crohn's drugs, it will decipher monoclonal antibody names for all conditions. You can also try creating your own names, like humungofungomab!

October summary of biologics

Medscape [direct link requires subscription] has released a new summary of the latest findings in biologic therapy for Crohn's disease. Their previous summary on recent anti-TNF research was in June. Although that's still well worth reading, there have been much activity in this area since then.

This article discusses combination therapies, first-line therapy (i.e. should biologics be used earlier in the treatment regime), switching biologics if they become ineffective, safety and newer biologics which have only recently been approved for use. Most of these have been reported in detail previously, but it's handy to have them summarised in one place.

A missing bacterium?

According to the BBC French researchers suspect that a low level of Faecalibacterium prausnitzii bacteria in the intestine could be the cause of Crohn's disease.

The researchers, from the Institut National de la Recherche Agronomique, had already shown that patients with Crohn's disease have a marked deficiency in bacteria from the Clostridium leptum group.

Their latest work shows that F. prausnitzii - a major component of this group - accounts for a large part of the deficit.

If this is true, then treatment would be a simple course of specific probiotics to boost the levels of the bacteria. However, this research is only at the level of cells in test tube. It still has the difficult hurdles of animal and human trials to come.

It's interesting to note that probiotics and antibiotics are both being proposed as possible cures for Crohn's. Although this sounds contradictory, they could both be successful. The probiotic may encourage the growth of certain "good" bacteria which work against "bad" bacteria, whereas the antibiotic works solely on eliminating the "bad" bacteria.

Infliximab more effective than Azathioprine

The Associated Press reports on research that shows Infliximab (Remicade), used alone or in combination with Azathioprine (Imuran) is significantly more effective, and no less safe, than a treatment of just Azathioprine.

Currently, doctors usually prescribe Azathioprine first, and only progress to Infliximab when that fails. This study indicates that Infliximab should be considered earlier. (Note that this study was financed and run by the producer of Infliximab.)

There is more coverage at MedPage Today.