Potential new drug for the treatment of sickle cell disease

Sep 13 2004

Medinox announces today the results of a preclinical study of a new drug (MX-1520) that shows a potent ansickling effect.

The results were published in the June 2004 issue of The British Journal of Haematology (BJH). MX-1520 is a prodrug of vanillin, a very popular food additive generally regarded as safe (GRAS) by the FDA. Thirty years ago, Dr. Donald Abraham discovered that the addition of a small amount of vanillin to a suspension of sickle erythrocytes obtained from patients with sickle cell disease prevented the sickling of red blood cells under hypoxia. However, vanillin has no therapeutic effect when taken orally because it is broken down in the upper gastrointestinal (GI) tract.

In order to prevent the destruction of vanillin in the GI tract, Medinox produced a variant of vanillin (MX-1520) by attaching a unique "linker" to the vanillin molecule. Researchers at the Company demonstrated that upon oral administration to rats, MX-1520 moves through the GI tract intact and is absorbed into the bloodstream. Once MX-1520 enters the bloodstream, it is biotransformed to vanillin, which easily passes through the red blood cell membrane, binds with sickle hemoglobin and prevents cell sickling.

According to the BJH article, when given orally to transgenic sickle cell mice, MX-1520 significantly reduced the percentage of sickled cells in the blood. Transgenic sickle mice that were administered MX-1520 lived nearly five times longer than mice that did not receive the drug when exposed to hypoxic conditions.

In the U.S., 80,000-100,000 people suffer from sickle cell anemia, an inherited blood disease that can cause episodes of severe pain, damage to vital organs, and death. Expenditures for sickle cell complications each year are a major burden to the U.S. healthcare system and are estimated at $1.5+ billion annually. As many as four million patients worldwide suffer from sickle cell disease. Although a variety of drugs are used to treat sickle cell disease, none has proven to be particularly effective. Many are too toxic to be used by children, who tend to experience high numbers of sickling-dependent vaso-occlusive episodes.

"There is still no safe and efficacious drug for treating patients, particularly children, with sickle cell disease," said Monte Lai, Ph.D., and CEO of Medinox. He added, "MX-1520 may be the breakthrough we need to provide an oral drug for the treatment of this disease."

Dr. Toshio Asakura at The Children's Hospital of Philadelphia, who is the senior author of the paper and who is the Director of the National Heart, Lung and Blood Institute Sickle Cell Disease Reference Laboratory, commented, "I am pleased that MX-1520 surmounts the difficulty of achieving vanillin bioavailability. I have been performing research in the field of sickle cell disease for over thirty years. I am grateful to Medinox for its persistence in attempting to develop a therapeutic approach that may help patients with sickle cell disease in the near future."

MX-1520 was developed as part of the Company's prodrug program, which also includes novel non-steroidal anti-inflammatory drugs (NSAIDs) with gastrointestinal-sparing properties. Medinox is the leader in anti-nitric oxide therapeutics and is developing a broad technology platform to address a wide variety of unmet medical needs including septic shock, acute respiratory distress syndrome (ARDS) and hemorrhagic shock.