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Examples of gastrointestinal diseases

Modified bacteria against Crohn's disease
Chronic intestinal inflammations like Crohn’s disease have serious consequences. The culprit is an overactive immune system, which wrongly directs inflammatory factors to the intestines. This causes tissue damage, which in turn produces symptoms like diarrhoea, stomach cramps, anaemia and fever. Researchers are trying to limit the harm done, by administering the antiinflammatory cytokine IL-10. But how can we ensure that this substance reaches the intestines in sufficient quantities? The answer is being sought in modified lactic acid bacteria, which travel via the stomach to the gut, where they release IL-10. A small-scale study has shown that this method is safe, but further research is needed to confirm whether or not it is sufficiently effective.

Gene therapy
Some congenital liver diseases can only be treated with a transplant. This is not an ideal solution, however, since the number of donor organs is limited and patients have to take immunosuppressant medication for the rest of their lives. An alternative might be gene therapy, at least if the condition concerned is caused by just a single defective gene. And this is indeed the case with the rare Crigler–Najjar syndrome. Patients lack the enzyme that is responsible for conjugating bilirubin. Research with Gunn rats – which naturally lack the enzyme that is also missing in Crigler–Najjar patients – has proven in principle that gene therapy can be used to correct the defect in question. Preparations are now underway for the first clinical trial in people with an advanced form of the disease. Crigler–Najjar itself is rare, but if the method works it may eventually be usable to treat other, more common liver conditions.

Examples of metabolic disorders

Thyroxine injections in the hypothalamus
The thyroid hormone thyroxine has a wide range of metabolic effects. For example, too much of it increases the liver’s glucose production whilst reducing sensitivity to insulin (thyrotoxicosis). This was seen as resulting from the effects of thyroxine on the liver, but it has now been found that the insulin resistance is partly caused by changes to the innervation of the liver itself through the sympathetic and parasympathetic nerves. The hypothesis that the metabolic changes in the thyrotoxicosis are partially the result of the effects of thyroxine on the brain, and in particular the hypothalamus, has recently been confirmed. It was found that glucose production in the liver of the rat increases substantially when thyroxine is administered directly to the hypothalamus, regardless of the thyroxine in the blood.

Gaucher’s disease
Gaucher’s disease is a rare condition that enlarges the spleen and liver: only about 150 patients in the Netherlands are receiving treatment for it. That obviously makes research more difficult. Nevertheless, a treatment for this condition has existed since the early 1990s: intravenous administration of the enzyme glucosidase (glucocerebrosidase). Although this works well with many patients, some do not benefit from it. The hope for them now lies in ‘small compounds’, which regulate the structure of bodily fats. Medicines to treat other storage disorders are also being sought. Studies that looked at enzyme therapy for Fabry’s disease and MPS I have recently been completed. The results are disappointing when treatment starts late, so early diagnosis is crucial.