EMBARGOED UNTIL OCT 22
Media contact: Janice Elkins or Sandra Henry (713 500 3030) Phone: (713) 500 3033 Pager: (713) 990 2649 E-mail: [email protected]
HOUSTON -- (October 22, 1997) -- Research at The University of Texas-Houston Health Science Center may help reduce the estimated 1.6 million deaths attributed each year to the malaria parasite Plasmodium falciparum. A $1.1 million grant from the National Institutes of Health awarded Sept. 30, will enable scientists to determine whether a blood factor common in African Americans, but rare among Caucasians, confers protection against the most severe form of the disease.
In a four-year study led by JoAnn Moulds, Ph.D., division of rheumatology and clinical immunogenetics, department of internal medicine, UT-Houston Medical School, researchers hope to explain the link between certain blood-group factors and changes in red cells that can lead to fatal blockages in blood vessels. This grant will enable comparison between previous findings from artificially-infected cells, and actual blood samples collected from malaria sufferers in Africa. If their hypothesis is correct and Moulds and her collaborators demonstrate a direct relationship between specific blood factors and susceptibility to severe malaria, the work could spawn new therapies which drastically reduce mortality rates.
Moulds explains: "Our earlier work, published in Nature in July, described how red blood cells infected with Plasmodium falciparum adhere to normal cells, forming 'rosettes' that promote the spread of infection and cause life-threatening blockages. The underlying cause seems to be the interaction of two proteins, PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1) and complement receptor one (CR1). We found that individuals with a particular form, a polymorphism, of the CR1 protein are less prone to rosetting, and so less likely to develop the most severe form of malaria. An estimated 30-40 percent of African Americans possess this 'protective' form of CR1, while the incidence among caucasians is about one percent. The implications of these findings are very exciting. Others have cloned the CR1 gene, raising the possibility of developing drugs which block the rosetting mechanism. But, would our results obtained from artificially infected cells be replicated in!
blood samples taken from people known to have the disease? By studying a large database of DNA samples from infected individuals in Kenya and Gambia, we hope to answer this crucial question."
The research is designed to determine which, if any, forms of the proteins under investigation protect against rosetting. In addition to the initial two, DNA sequence analysis has revealed a further 10 genetic polymorphisms. The role of these proteins in malaria rosetting will be determined by collaborator Alexandra Rowe, Ph.D., working at John Radcliffe Hospital in Oxford, England. Rowe was the first to describe this phenomenon and clone the PfEMP1 protein. Moulds and co-principal investigator Peter Zimmerman, Ph.D., of Case Western Reserve University, will analyze the approximately 1000 blood samples, identifying the protein profile of each individual using DNA analysis. This work will be done both in Oxford, where the DNA database is located, and Moulds' laboratory at UT-Houston. The study draws heavily on work begun by Louis Miller, Ph.D., of the NIH Laboratory of Parasitic Diseases. A 30-year veteran of malaria research, Miller is scientific consultant to the project group.
At the conclusion of the study, the team hopes to have formulated a method of genetic-typing -- a simple blood test -- that will identify individuals prone to severe malaria. It may then be possible to administer a 'blocking agent', such as an artificially-produced protein, that prevents the potentially deadly formation of red blood cell rosettes. It is known that if malaria sufferers can survive this stage of the disease, they develop antibodies which ameliorate against its worst effects. Therefore, any therapy proven to prevent rosetting may reduce the devastating mortality rate that makes this form of malaria the world's most deadly disease.
Note to media - Dr. Moulds is out of the office until Thursday Oct 23
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