Breakthrough in search for new anti-malarial drugs

Scientists at Drexel University College of Medicine in Philadelphia have made a significant discovery in the fight against malaria. Drexel researchers, along with a research group at the University of Washington, have determined a critical molecular structure of the cellular motor that allows the malaria parasite to invade human cells.

This breakthrough could lead to the development of newer and much needed anti-malarial drugs.

"Our findings have the potential to be very significant on several fronts," said Lawrence W. Bergman, Ph.D., Professor of Microbiology and Immunology at Drexel University College of Medicine. "Having determined the atomic structure of a key motor complex that is absolutely required for the parasite to enter cells, we can begin a process called structure-guided drug design."

Approximately 300 million people worldwide are affected by malaria and one million to three million die from it each year. In recent years, concern has grown over an increase in resistance to drugs normally used to combat the parasite that causes the disease. In fact, experts recently warned that a global malaria "superbug" is now at risk of development.

Malaria parasites are transmitted to people through a bite from an infected mosquito. The parasite travels in a person's body, invades the liver and then red blood cells, producing billions of progeny that destroy red blood cells.

Dr. Bergman and the Drexel team, along with the UW group led by Dr. Wim Hol, were able to identify two proteins critical to the malaria invasion. They determined that one muscle cell protein known as MyoA interacts with another protein known as MTIP forming a complex that is critical for the parasite to gain entry into blood and liver cells.

"This is the first time that the structure of these molecules was determined in such fine detail," said Dr. Bergman. "Just as important, we also demonstrated that these molecules were a target for chemotherapeutic intervention."

The Drexel scientists were also able to show that a reagent directed against the complex blocked the growth of the parasite in human red blood cells in the laboratory.

"Since this complex is needed for all life stages of the parasite, if a drug was developed against the complex, it would not only lessen the disease if taken by a person already infected, but could also block infection of an uninfected person," said Dr. Bergman.

The findings are available in the online edition of the Proceedings of the National Academy of Sciences.