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.