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).