Still waiting for a magic pill

A few years ago it looked like antibiotics treating MAP would be effective in attacking the cause of Crohn's disease. Early trials had been very effective in producing and maintaining remission. However, not much was heard about later, larger trials.

Giaconda, the company which now owns the rights to this therapy, have published a summary of the details so far.

The results of a Phase II clinical trial of Myoconda®, conducted at the Centre for Digestive Diseases (CDD), were published in 2002. This was followed up with a full retrospective analysis of all CDD Crohn’s patients treated for at least six months with anti-MAP therapy. This analysis of 52 patients demonstrated a remission rate of 65% with a clinical response of almost 95%. These results exceed those of any Crohn’s therapy on the market by major margins.
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[A Phase III] trial was completed in September 2004. Overall results of the Phase IIIa trial demonstrated a statistically significant improvement in achieving remission at 16 weeks when using Myoconda® compared with conventional therapy. However, Myoconda® did not achieve statistically significant results in maintaining remission after therapy was complete in this trial.

They do not say whether the lack of remission was due to the antibiotics failing to prevent MAP, or whether the MAP was successfully eliminated but the Crohn's remained. However, since they are continuing their testing of variants of this treatment, it appears that it is the former, which means that the theory of MAP being a cause of Crohn's is still alive.

(CC-licensed image by Rodrigo Senna)

Gene therapy moves closer

A report from the Royal Society of Chemistry describes a potential new treatment for Crohn's that has shown promise in mice. RNA interference, a recently developed method of gene therapy, was used to suppress a gene that causes inflammation in the intestine, thus reducing the related symptoms.

RNA interference involves introducing into cells a double strand of RNA corresponding to the nucleic acid sequence of the target gene. This causes the destruction of the equivalent messenger RNA so 'silencing' the gene and preventing expression of the relevant protein.

Its discovery in 1998 by Andrew Fire and Craig Mello earned them the 2006 Nobel prize for medicine. But although their discovery has become a vital technique for molecular biology research it has not yet fulfilled its potential as a therapeutic method.
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When RNA was injected into mouse with colitis there was a dramatic reduction in intestinal tissue damage and suppression of leukocytes cells invading the gut wall. The mice were also able to absorb food through their gut wall again and started to regain weight. The team found that their results were due to a drop in the level of two cell signalling molecules (cytokines), TNF-alpha and IL-12, that normally drive inflammation and are produced as a result of cyclin D1 synthesis. They also found that the mice were making more of a protective cytokine called IL-10.

There is a long way to go until this research leads to a safe treatment in humans. For example, at this time not all of the genes involved in Crohn's have been identified. I'm sure that gene therapy would want to be as specific as possible to reduce unintended side-effects.