Vanilla May Have a Future as a Sickle Cell Treatment

09/20/2004

PHILADELPHIA, Sept. 20 /PRNewswire/ -- 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.

The National Institutes of Health and the Mizuno Fund at The Children's Hospital of Philadelphia supported the study. Co-authors with Dr. Asakura were Chaojie Zhang, Xiang Li, Lurong Lian, Qiukan Chen, and Osheiza Abdulmalik, of
Children's Hospital, and Vasco Vassilev and Ching-San Lai of Medinox, Inc.
Medinox supplied the MX-1520 used in the study.

About programs for sickle cell disease at The Children's Hospital of Philadelphia: Established in 1988 and supported by the National Institutes of Health (NIH), The Comprehensive Sickle Cell Center at Children's Hospital is one of only 10 such programs in the United States, and engages in basic and clinical research as well as public education on sickle cell disease and related hemoglobin disorders. Children's Hospital also houses a full clinical program for sickle cell disease, providing screening, care, education and counseling to patients and their families. The Sickle Cell Disease Reference Laboratory was established at Children's Hospital by the National Heart, Lung and Blood Institute of the NIH to provide rapid, efficient, accurate and
economical evaluation of agents or therapies that may benefit patients with
sickle cell disease. Since its inception in 1997, the laboratory has received
more than 75 candidate drugs for evaluation.

Founded in 1855 as the nation's first pediatric hospital, The Children's Hospital of Philadelphia is ranked today as the best pediatric hospital in the nation by U.S.News & World Report and Child magazine. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service
programs have brought the 430-bed hospital recognition as a leading advocate
for children and adolescents from before birth through age 19. For more
information, visit http://www.chop.edu.

CONTACT: John Ascenzi, The Children's Hospital of Philadelphia, +1-267-426-6055, Ascenzi@email.chop.edu.