Research, without using animals I presume

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Molecular models advance the fight against malaria

26 Apr 2005

 

 

 

 

 

Research from Dartmouth Medical School, demonstrating how malaria

parasites form mutations that make them stubbornly resistant to drug

therapy, may hold the key to a new treatments for a disease that

afflicts more than half a billion people worldwide.

 

The scientists developed disease models using yeast and successfully

introduced five mutations that make malaria resistant to the anti-

malarial drug, atovaquone. The study, featured as the cover story of

the April 29 Journal of Biological Chemistry, paves the way for using

these models to test new drugs that could suppress malaria's ability

to mutate against current therapy. " This is the first quantitative

explanation for malaria's drug resistance, " said Dr. Bernard

Trumpower, professor of biochemistry at Dartmouth Medical School and

head of the study. " In addition to confirming the belief that the

resistance was due to these mutations, we have created a practical

research tool to design new, improved versions of the drug using

these resistant strains. "

 

Malaria, transmitted by Plasmodium falciparum, a parasite carried by

mosquitoes, has developed resistance to almost every anti-malarial

drug introduced in the past 30 years. Although atovaquone is one of

the most recent drugs on the market, there is significant evidence

that malaria parasites are quickly developing resistance to that drug

as well. According to WHO estimates, 40% of the world's population

are currently at risk of the disease and approximately 2 million

people, mostly children, are killed by malaria annually worldwide.

Today marks Africa Malaria Day, organized to promote awareness of the

disease in a country where a child is killed every 30 seconds by

malaria.

 

Investigating ways to counter the mutations and sustain the efficacy

of anti-malarial drugs, Trumpower and his colleagues continued their

work on previous studies using yeast enzymes to explore atovaquone

resistance. It is not possible to grow enough malaria parasites to

isolate and study the respiratory enzyme cytochrome bc1 complex,

which the parasites need to live and multiply. A protein subunit of

the bc1 complex is where the malaria parasite mutates to counter anti-

malarial drug therapies. Yeast is an effective resource because it

can be safely grown in large quantities and can be easily modified to

take on the qualities of more dangerous pathogens, without risking

human infection.

 

When the researchers genetically transferred mutations into the yeast

surrogates, the yeast acquired resistance to atovaquone just as the

malaria parasites had done. The team was then able to apply

computerized modeling techniques to illustrate exactly how the drug

interacted with the cytochrome bc1 complex - the respiratory enzyme

the parasites need to live and multiply -- on a molecular level. With

this new understanding of how the parasites were able to counter the

effects of atovaquone, researchers can now design new anti-malarial

drugs with features making the appearance of resistance more

unlikely.

 

" Within the next 3-5 years, we hope to develop a new drug that will

finally empower us to treat this terrible disease, " said Trumpower.

 

Dartmouth Medical School co-authors of the paper are Dr. Jacques

Kessl, research associate in biochemistry, Kevin Ha, Anne Merritt and

Benjamin Lange. Other co-authors are Dr. Brigitte Meunier and Philip

Hill from the Wolfson Institute for Biomedical Research in London and

Dr. Steven Meshnick from the University of North Carolina, Chapel

Hill.

 

Contact: Andrew Nordhoff

mednews

603-650-1492

Dartmouth Medical School

http://www.dartmouth.edu