Articles about new Celiac Disease drugs, treatment methods etc.

New Therapy May Mean Less Dietary Restrictions For Celiac Sufferers

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27 Jun 2006

Scientists have discovered what may be a successful non-dietary therapy for celiac sprue, an inherited inflammatory disorder of the small intestine that impacts an estimated 1 in 200 people around the world. Two research studies, published in the June issue of Chemistry and Biology, pave the way for clinical testing with an oral enzyme therapy that may prevent the many symptoms and complications of this widespread disease.

People with celiac sprue, also called celiac disease, cannot tolerate the protein gluten in their diet. Gluten is present in grains like wheat, barley, and rye. When gluten is ingested by a celiac patient, it sets off an inflammatory reaction that damages the small intestine, leading to malabsorption, an autoimmune-like response, and many other complications. The only effective therapy for celiac disease is complete dietary exclusion of gluten. However, the ubiquitous nature of gluten poses a constant threat to celiacs, and a majority of celiac patients who adopt a restrictive diet still exhibit structural and functional gut abnormalities.

"Non-dietary therapies that allow celiac patients to safely incorporate low-to-moderate levels of gluten into their daily diet would be of considerable benefit," explains study leader Dr. Chaitan Khosla, from Stanford University and Celiac Sprue Research Foundation. "Having demonstrated earlier that certain types of enzymes can detoxify gluten, our laboratory set out to devise an optimal oral enzyme therapy for celiac sprue by borrowing from nature. In germinating barley seed, gluten serves as a nutritious storage protein that is efficiently digested by enzymes. One enzyme, EP-B2, plays a crucial role in this process by breaking gluten proteins after glutamine residues, which comprise one-third of all amino acid residues in gluten."

Dr. Khosla's group used recombinant bacteria to produce a form of EP-B2 that only activates under acidic conditions similar to the conditions found in the human stomach. The researchers demonstrated that EP-B2 efficiently digested gluten protein under gastric conditions and, importantly, EP-B2 was most specific for those parts of gluten that are known to trigger celiac pathogenesis. In a second study, the researchers went on to devise an even more potent double enzyme therapy for detoxifying gluten.

EP-B2 was tested in combination with another well-characterized enzyme called PEP that breaks gluten protein after proline residues. Like glutamine, proline is also abundant in inflammatory gluten peptides. At very high gluten loads, where neither PEP nor EP-B2 alone could detoxify gluten quickly enough to prevent inflammation, a PEP and EP-B2 combination completely abolished gluten immunotoxicity within ten minutes under simulated gastric and duodenal conditions.

In this tag-team therapy, EP-B2 first cleaved gluten into small pieces under gastric conditions that were then easier for PEP to fully detoxify under duodenal conditions. "Our results suggest that recombinant EP-B2 should be effective as supportive therapy to help celiacs cope with the 'hidden' gluten in everyday life, and that a two-enzyme cocktail containing PEP and EP-B2 may even allow celiacs to resume a more normal diet in the future," offers Dr. Khosla.
http://www.medilexicon.com/medicalnews.php?newsid=45935∞

Understanding The Immune Response To Forbidden Foods In Celiac Disease

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30 Jul 2006

Individuals who suffer from the chronic autoimmune condition celiac disease possess serum antibodies to gluten, a protein found in wheat, barley and rye, causing a wasting away of the small intestine and poor absorption of nutrients. Currently, the only effective treatment is the life-long elimination of gluten from the diet. Antibodies to the enzyme tissue transglutaminase are found in an overwhelming majority of cases, and cross-react to gluten. This reaction occurs almost exclusively in patients with the human leukocyte antigen types HLA-DQ2 and HLA-DQ8. Over 95% of celiac patients carry 1 or 2 of the HLA-DQ2 or HLA-DQ8 genes.

In a study appearing online in July, in advance of print publication in the August issue of the Journal of Clinical Investigation, Ludvig Sollid and colleagues from the University of Oslo used intestinal T cells from celiac patients to locate DQ2 and DQ8 binding sites (known as epitopes) within 2 gluten proteins - alpha-gliadin and gamma-gliadin. The authors show that DQ2 and DQ8 are preferentially triggered by deamidated peptides and have a preference for binding to negatively charged residues in the gluten proteins. In addition, the authors examine the similarities and differences between peptides recognized by these two molecularly distinct DQ molecules and their association with disease susceptibility. These insights will aid our understanding of the immunopathology of celiac disease and are broadly relevant to the mechanisms of immune recognition at work in other autoimmune diseases.
http://www.medilexicon.com/medicalnews.php?newsid=48298∞

Potential Link Between Celiac Disease And Cognitive Decline Discovered By Mayo Clinic

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11 Oct 2006

Mayo Clinic researchers have uncovered a new link between celiac disease, a digestive condition triggered by consumption of gluten, and dementia or other forms of cognitive decline. The investigators' case series analysis -- an examination of medical histories of a group of patients with a common problem -- of 13 patients will be published in the October issue of Archives of Neurology.

"There has been very little known about this connection between celiac disease and cognitive decline until now," says Keith Josephs, M.D., Mayo Clinic neurologist and study investigator. "This is the largest case series to date of patients demonstrating cognitive decline within two years of the onset of celiac disease symptom onset or worsening."

Says Joseph Murray, M.D., Mayo Clinic gastroenterologist and study investigator, "There has been a fair amount written before about celiac disease and neurological issues like peripheral neuropathy (nerve problems causing numbness or pain) or balance problems, but this degree of brain problem -- the cognitive decline we've found here -- has not been recognized before. I was not expecting there would be so many celiac disease patients with cognitive decline."

The next step in the research will be to investigate the measure and nature of the connection between the two conditions.

"It's possible it's a chance connection, but given the temporal link between the celiac symptoms starting or worsening and the cognitive decline within a two-year time span, especially the simultaneous occurrence in five patients, this is unlikely a chance connection," says Dr. Josephs. "Also, these patients are relatively young to have dementia."

Theories to explain the connection between celiac disease and cognitive decline include the following, according to Dr. Murray:

* Nutritional deficiency

* Inflammatory cytokines -- chemical messengers of inflammation that could contribute to problems in the brain

* An immune attack on the brain that may occur in some patients with celiac disease

The cognitive decline that occurred in three of the celiac disease patients studied, according to Dr. Josephs, is relatively unique in its reversal in two of the patients and stabilization in one patient. Typically, cognitive decline continues to worsen, he says. "This is key that we may have discovered a reversible form of cognitive impairment," he says.

William Hu, M.D., Ph.D., Mayo Clinic neurology resident and study investigator, says that the reversal or stabilization of the cognitive symptoms in some patients when they underwent gluten withdrawal also argues against chance as an explanation of the link between celiac disease and cognitive decline.

Currently, the investigators do not know which celiac disease patients are at risk for cognitive decline; this deserves future investigation, says Dr. Hu.

Dr. Murray suggests that recognizing and treating celiac disease early will likely prevent most consequences of the disease, including symptoms in the gut or the brain. For celiac disease patients who have already developed cognitive decline, closely following a gluten-free diet may result in some symptom improvement, he says. For those with cognitive decline without a confirmed diagnosis of celiac disease, he does not recommend a gluten-free diet, however.

Physicians can play an important role in keeping alert to a potential celiac disease and cognitive decline connection, says Dr. Hu.

"For patients who come in with atypical forms of dementia, we need to consider checking for celiac disease, especially if the patients have diarrhea, weight loss or a younger age of onset -- under age 70," he says.

To conduct this case series analysis, the researchers identified 13 Mayo Clinic patients with documented cognitive impairment within two years of onset of symptoms or severe exacerbation of adult celiac disease. All celiac disease had been confirmed by small-bowel biopsy, and any patients for whom an alternate cause of cognitive decline could be identified were excluded from the analysis. Patients included five women and eight men, with a median onset of cognitive decline at age 64 that coincided with onset or worsening of symptoms of diarrhea, the presence of excess fat in the stools and abdominal cramping in five patients. The most common reasons for seeking medical help were amnesia, confusion and personality changes. The average score on the Short Test of Mental Status among the 13 patients was 28 out of 38 possible total, indicating moderate cognitive impairment. Ten patients experienced loss of coordination and four experienced symptoms of peripheral neuropathy. Four patients demonstrated deficiency in folate, vitamin B-12, vitamin E or a combination of these deficiencies, although supplementation did not improve the patients' cognitive decline. Three patients' cognitive decline either improved or stabilized when they completely withdrew from gluten consumption. A brain autopsy or biopsy was completed in five patients, and there was no evidence of Alzheimer's disease or any other well-known causes for dementia.

Celiac disease occurs in 1 out of 133 people and predominantly affects Caucasians, according to Dr. Murray. Symptoms can include intermittent diarrhea, abdominal pain and bloating, or no gastrointestinal symptoms at all. It can also manifest in weight loss, fatigue, anemia, general weakness, foul-smelling or grayish stools that may be fatty or oily, osteoporosis or stunted growth (in children only). The condition may also cause symptoms far outside of the gut. Nine out of 10 times, the disease is not discovered due to the vague nature of the symptoms, according to Dr. Murray. The treatment for celiac disease is a gluten-free diet. For further information on celiac disease, see http://www.mayoclinic.com/health/celiac-disease/DS00319∞
http://www.medilexicon.com/medicalnews.php?newsid=53741∞

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