Dr. Margaret Phillips

By Heather Svokos

Malaria is still one of the world’s major infectious disease killers. Transmitted through mosquitoes, it claims nearly 450,000 lives worldwide each year. Many of its victims are pregnant women and children under the age of 5. Nearly 200 million cases are reported annually, and about 3 billion people are at risk of malaria in 97 countries.

Malaria was eradicated in the United States in 1951. Yet it remains a menace in many parts of the world today, because as each promising or successful treatment emerges, it is eventually thwarted by the development of drug resistance.

In what appears to be a major breakthrough, researchers at UT Southwestern Medical Center have found that a drug currently in testing has the potential to cure malaria in a single dose, and also offers promise as a preventive treatment.

The new drug – DSM265 – kills drug-resistant malaria parasites in the blood and liver by targeting their ability to replicate, said the study’s lead scientist, Dr. Margaret Phillips, Professor of Pharmacology at UT Southwestern. 

Currently, the front-line antimalarial treatments are artemisinin-based combination therapies, or ACTs, which are credited with helping to reduce the malaria burden. However, malaria strains resistant to ACTs have recently been reported in Thailand, Cambodia, Vietnam, Myanmar, and Laos.

“People are dying of a curable disease in large numbers, and that’s the tragedy. We’re making progress, because 10 years ago, 1 million people were dying of malaria and the number has steadily dropped by more than half,” said Dr. Phillips, who joined the UT Southwestern faculty in 1992 as an Assistant Professor.

The problem, Dr. Phillips said, is that scientists are starting to see more drug resistance in the current treatments, which is what has rendered previous anti-malarial drugs useless.

In order to combat drug resistance, DSM265 likely would be partnered with another new drug and used as a one-dose combination therapy. Another option is to develop DSM265 as a once-weekly preventive treatment for individuals traveling to malaria-endemic regions or for people living in areas where malaria infections are primarily seasonal and human immunity is low. Either scenario is still several years away, pending the outcome of current and future trials, said Dr. Phillips.

Work on the project leading to the discovery of DSM265 began in Dr. Phillips’ lab in 2003. The research team included UT Southwestern, the Monash Institute of Pharmaceutical Sciences in Australia, the University of Washington, and the not-for-profit Medicines for Malaria Venture (MMV). In 2010, the project team received the Project of the Year Award from MMV for the discovery of DSM265.

“For me personally, the opportunity to see my research potentially impact patients is the most rewarding experience of my career,” Dr. Phillips said. “If, in the end, the drug receives FDA approval, it will be a major accomplishment, and UT Southwestern will have contributed to the prevention of a dreaded, often deadly disease.”

Dr. Phillips has been a Professor of Pharmacology at UT Southwestern since 2002. She received her Bachelor of Science degree in biochemistry from the University of California, Davis in 1981 and her Ph.D. in pharmaceutical chemistry from the University of California, San Francisco (UCSF) in 1988, where she began her work on another protozoal pathogen, African sleeping sickness, in the lab of Dr. C.C. Wang. Dr. Phillips was then a postdoctoral fellow in the lab of Dr. William Rutter at UCSF until 1992.

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Dr. Phillips holds the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science, and the Carolyn R. Bacon Professorship in Medical Science and Education.