Thursday, March 28, 2024 | Ramadan 17, 1445 H
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EDITOR IN CHIEF- ABDULLAH BIN SALIM AL SHUEILI

Are We Close to a Cure for Celiac Disease?

SCI-CELIAC-DISEASE
SCI-CELIAC-DISEASE
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Until about 15 years ago, pharmaceutical companies showed little interest in drug development for celiac disease, said Dr Alessio Fasano, director of the Center for Celiac Research and Treatment at Massachusetts General Hospital in Boston. At the time, researchers knew that for those with the condition, consuming gluten — a protein found in wheat, rye and barley — caused damage to the small intestine. But they didn’t understand how or why gluten had this effect. And, Fasano said, it seemed there was already a simple way to manage celiac disease: adopt a gluten-free diet.


For the estimated 1% of people who have this autoimmune condition, avoiding gluten is the only method for thwarting small intestine damage and relieving the various symptoms of the disease, which can include abdominal pain, diarrhoea, constipation, depression, fatigue, headache, a blistery skin rash and iron-deficiency anaemia.


But consuming even minuscule amounts of gluten — just a breadcrumb from a cutting board, for example — can re-trigger symptoms and intestinal damage. And maintaining a strict gluten-free diet in a world full of hidden gluten-containing ingredients requires constant vigilance and makes eating out, travelling and going to school risky and anxiety-provoking, Fasano said.


In a survey published in 2014, 341 people with celiac disease rated the burden of managing their condition as worse than those who had chronic acid reflux or high blood pressure, and similar to those who lived with diabetes or kidney disease that required dialysis. Despite trying to avoid gluten, as many as 30% of people with celiac disease still have symptoms, said Dr Elena Verdú, a professor of gastroenterology at McMaster University in Ontario.


Gluten-free foods can also be more expensive than their gluten-containing counterparts, and many people don’t have access to the support of a dietitian to help them plan a balanced, gluten-free diet, Verdú said.


As it’s become clearer that maintaining a gluten-free diet is neither simple nor satisfactory for many celiac patients, researchers have also made recent strides in grasping how the disease works. We now understand “almost step-by-step the march, the progress from the moment in which you break down gluten to the point in which you destroy your intestine,” Fasano said. “An entire world opens up in terms of new treatments.”


There are 24 potential therapies at various stages of development, according to the Celiac Disease Foundation. Those being tested target different steps in the disease pathway, Fasano said. Some are enzymes meant to improve the digestion of gluten, breaking it down into smaller, less harmful fragments. Other approaches make the lining of the small intestine less porous, so that it’s more difficult for partly digested gluten to enter the body. Still others target the immune system to prevent it from damaging the intestine in response to gluten, Fasano said.


If proved safe and effective, these potential therapies probably would not be cures for celiac disease, but they could mitigate the effects of accidentally eating small amounts, Verdú said.


Still, they’re most likely at least a few years away from being approved. “Drug design and approval is a really very lengthy path,” said Verdú, whose clinic is participating in several trials but who does not have any financial ties to the drugs.


Of the potential therapies in development, the one furthest along — now being tested in a Phase 3 trial — is a drug called larazotide, which decreases the porosity of the small intestine. In a best-case scenario, larazotide could be approved and on the market within two to three years, said Fasano, who was involved with the development of the drug and has a financial interest in it.


But, he added, for every five or six drugs tested in Phase 3 trials, only one or two will be approved. Several other potential therapies are now in Phase 2 trials; which could be five to six years from market, Fasano said.


The cost of celiac therapies would vary. The larazotide and digestive enzyme treatments are relatively cheap — they “cost cents to produce,” Fasano said — but drugs targeting the immune or inflammatory response would be more expensive. — NYT


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