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Potential cure for coeliac disease

20-Feb-2003

Results from a new study may lead to the first medical treatment for coeliac disease, a hereditary digestive disease that can damage the small intestine and interfere with the absorption of nutrients from food.

Coeliac disease sufferers cannot tolerate gluten, a protein that is found in wheat, barley and rye, and there is no known medical treatment or cure.

Researchers from Zengen, a California-based biopharmaceutical company, discovered that a synthetic form of alpha-Melanocyte-Stimulating Hormone (alpha-MSH) has an anti-inflammatory effect in coeliac mucosa, the inside lining of the intestinal tract that absorbs food into the body. A naturally occurring molecule, alpha-MSH modulates inflammatory and immune responses.

Data confirming the presence of alpha-MSH in coeliac mucosa suggests the presence of a local reaction of the molecule to control the inflammatory response elicited by gliadin. Gliadin is the subfraction of gluten that acts as a toxin or poison in people with coeliac disease; it causes an immune reaction, resulting in damage to the small intestine and an inability to digest and absorb nutrients necessary for health and growth (malabsorption).

"Our research suggests that locally-produced alpha-MSH modulates inflammation and perhaps limits epithelial damage in patients with coeliac disease," said James Lipton, study investigator and chief scientific officer and director of Zengen. "We are particularly excited by these findings as these data, coupled with abundant evidence of the anti-inflammatory and anti-infective activity of Zengen's novel molecules based on alpha-MSH, further validate our research and development efforts in numerous areas including coeliac disease. These positive results will be used to guide further advancements toward clinical use of the molecules."

The study used human coeliac mucosa cells in culture. Researchers collected duodenal biopsy pairs from 53 adult coeliac patients (34 untreated patients and 19 coeliac patients on a gluten-free diet) and 14 normal subjects and conducted three series of experiments in order to determine three factors. Firstly, the researchers tested mucosal immunoreactivity for alpha-MSH and melanocortin receptors (MCRs), as well as gene expression of alpha-MSH precursor pro-opiomelanocortin and MCRs. Secondly, they investigated alpha-MSH and inflammatory cytokine production by duodenal specimens in vitro, and the influence of synthetic alpha-MSH on such cytokine production. Finally, the study focused on the influence of stimulation with gliadin on alpha-MSH and cytokine production in vitro and the effect of alpha-MSH on gliadin-stimulated cytokine production.

According to the researchers, the results suggested a localised anti-inflammatory influence based on alpha-MSH and its receptors. In addition, alpha-MSH and MC1R immunoreactivity was more intense in cell specimens from coeliac patients and release of interleukin 6 (a lymphokine that stimulates the inflammatory response) from gliadin-stimulated duodenal mucosa was inhibited by synthetic alpha-MSH.

"Patients suffering from coeliac disease currently have no medical options beyond a lifetime adherence to a strict, gluten-free diet," added Dr. Lipton. If left untreated, coeliac disease can lead to malabsorption, which, in turn, can lead to malnutrition. The disease is especially serious in children and adolescents, who need adequate nutrition to develop properly. Furthermore, people with coeliac disease who do not maintain a strict, gluten-free diet have a greater chance of developing one of several forms of cancer, particularly intestinal lymphoma. Other long-term complications include anaemia, diabetes mellitus, hypothyroidism, osteoporosis, seizures and peripheral neuropathy.

"Clearly, if we can control the inflammatory responses that are a major part of coeliac disease and limit the immunosuppression, this could lead to the first medical treatment to help the millions worldwide suffering from this genetic disease," he concluded.

Full details of this research can be found in the February 20, 2003 issue of NeuroImmunoModulation, the official journal of the International Society for Neuroimmunomodulation. Article entitled "Anti-Inflammatory Effects of alpha-Melanocyte-Stimulating Hormone in Celiac Intestinal Mucosa."

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