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Vanilla may have a future in sickle cell treatment

21.09.2004


In addition to its popular role in flavoring ice cream, fudge and cake frosting, vanilla may have a future use as a medicine. Recent laboratory research has strengthened the possibility that a form of vanilla may become a drug to treat sickle cell disease.


After specially bred mice received a compound that turns into vanilla in the body, they survived five times longer than mice that did not receive the chemical. All the mice had been subjected to low oxygen pressure, a condition that causes their red blood cells to form the hazardous sickle shape. Results of the study, led by research hematologist Toshio Asakura, M.D., Ph.D., of The Children’s Hospital of Philadelphia, appeared in the June 2004 issue of the British Journal of Haematology.

It had been known for 30 years that vanillin, the compound that gives the vanilla bean its flavor, protects red blood cells with sickle cell disease from assuming the sickle shape that obstructs blood vessels. However, this effect previously occurred only in test tubes, because vanillin normally breaks down in the digestive tract before reaching the bloodstream.

Scientists at Medinox, a San Diego-based biotechnology company, developed a variant of vanillin called MX-1520, chemically modifying it to resist degradation by the digestive system. MX-1520 is a prodrug--a compound that becomes an active drug (in this case, vanillin) in the body.



Dr. Asakura and his team tested MX-1520 in the NIH-sponsored Sickle Cell Disease Reference Laboratory that he directs at The Children’s Hospital of Philadelphia. The researchers used transgenic sickle mice--animals with red blood cells containing human sickle hemoglobin, similar to the defective blood cells in people with sickle cell disease. The researchers found that most of the MX-1520 turned into vanillin in the mice, where it interacted with sickle hemoglobin and inhibited the formation of rigid sickled cells.

Sickle cell disease affects 80,000 patients in the United States and millions more throughout the world, predominantly in Africa, India, the Middle East and Mediterranean countries. Most of those affected by sickle cell disease are of African descent. A gene mutation causes red blood cells to become stiff and sickle-shaped, damaging and obstructing blood vessels. The disease may cause severe pain, stroke, anemia, life-threatening infections, and damage to the lungs and other organs.

Currently, only one drug, hydroxurea, is approved in the U.S. for treating sickle cell disease, but it is not effective for all patients, and it has adverse side effects such as suppressing bone marrow activity. "Clearly, we need to develop safer and more effective drugs for sickle cell disease," said Dr. Asakura. "By evaluating a variety of potential drugs, we hope to contribute to developing a range of drugs for different stages and different complications of the disease."

The results of his study, says Dr. Asakura, indicate that further study of the vanillin prodrug MX-1520 is warranted, but he stressed that the compound has not yet been studied in any patients. Patients with sickle cell disease should also be aware that this study does not imply that eating food products currently containing vanilla will benefit patients, because most vanilla is destroyed in the stomach and does not reach the bloodstream.

John Ascenzi | EurekAlert!
Further information:
http://www.chop.edu

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