Tuesday, 27 April 2010

Chrons Disease & Genetics

Whilst in the past, the search for a cure to Chrons Disease and other irritable-bowel conditions, the medical profession has mostly focused on diet. But recent studies have repeatedly failed to show that foods are to blame.

Researchers are now looking at genetic mutations linked to Crohn's Disease as well as other irritable bowel conditions like ulcerative colitis. They hope to develop a therapy that fixes those mutations in order to actually cure diseases like chrons and ulcerative colitis, rather than just treat the symptoms.

Warren Strober of the the National Institute of Allergy and Infectious Diseases in Bethesda has been studying these diseases for over fifteen years and he and other scientists have shown that dozens of genes are linked to Chrons and ulcerative colitis.

His current work centers on developing a stem-cell-based therapy to correct one particular gene mutation for Chrons. Because of the wide variety of mutations it means that there could eventually be a number of different treatments that target patients based on their genetic profiles, this is known as "personalized medicine."

People with Crohn's can suffer from chronic diarrhea, abdominal pain, fever, fatigue and sometimes rectal bleeding. They may also have problems absorbing an adequate amount of nutrients from food, particularly if too much of the intestine is removed. The disease can stunt the growth of children.

With irritable-bowel diseases, the immune system attacks harmless bacteria normally found in the gut. This response leads to inflammation of different parts of the digestive tract, which in turn can cause, fissures, abscesses, obstruction and pain.

In Chrons disease the walls of the digestive tract become inflamed, and any part from the mouth through to the large intestine can be affected. Ulcerative colitis is slightly different in that only the lining of the bowel is damaged.

Treatments have improved in recent years and now include powerful, injectable biologic medicines that reduce inflammation, such as Remicade and Humira.

But these are not cures, and not everyone responds to them. In severe cases, patients must undergo surgery sometimes multiple surgeries to remove parts of the bowel or colon that are blocked. For Chrons patients this is necessary more often because it can develop in any part of the gut, inflammation can recur even after surgery in a different segment of the digestive tract. Within 10 years after surgery between 80% and 90% of Chrons patients will have a relapse, according to researchers.

Dr. Strober says he and his colleagues, are moving ahead on research in mice that aims to fix a genetic mutation called NOD2 associated with Crohn's Disease. The idea would be to have the body repair itself by growing the corrected gene using so-called induced pluripotent stem cells.

Stem cells are those that can develop into different types of specialized cells, like heart or muscle cells, and are mostly found in embryos. Induced pluripotent stem cells, or iPS cells, are made by taking adult specialized cells and turning back the clock, engineering them to an earlier stage where they can reproduce again.

With his research they have already worked out how to take cells from the intestine and convert them into iPS cells. The team are now are working on fixing the genetic defect in the iPS cells before testing the therapy in animals.

The biggest challenge with this type of approach that combines genetic information, physical symptoms and biology is actually narrowing down which genetic combinations are critical to which patients.

Other researchers are examining how genetic mutations affect the type of bacteria that are found in the digestive tract. Greater presence of certain types of bacteria may be more likely to trigger an immune response.

Another area of research is looking at understanding how a persons genetic makeup can make them susceptible to certain other Chrons disease triggers like smoking or stress and the use of nonsteroidal anti-inflammatory painkillers.

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