February 10, 2015--(BRONX, NY)--Each year nearly 600,000 people--mostly children under age five and pregnant women in sub-Saharan Africa--die from malaria, caused by single-celled parasites that grow inside red blood cells. The most deadly malarial species--Plasmodium falciparum--has proven notoriously resistant to treatment efforts. But thanks to a novel approach developed by scientists at Albert Einstein College of Medicine of Yeshiva University and described in the January 20 online edition of ACS Chemical Biology, researchers can readily screen thousands of drugs to find those potentially able to kill P. falciparum.
Scientists have known for more than a decade that malaria parasites have an Achilles heel: Like all cells, they require two key building blocks--purines and pyrimidines--to synthesize their DNA and RNA. But malaria parasites can't synthesize purines on their own. Instead, they must import purines from the host red blood cells that they invade. A parasite protein called PfENT1 transports purines from blood cell into the parasites. So drugs that block PfENT1 could conceivably kill the parasites by depriving them of purines they need--but an experimental approach for identifying PfENT1 inhibitors didn't exist, until now.
Einstein's Myles Akabas, M.D., Ph.D., developed a novel yeast-based high-throughput assay for identifying inhibitors of the PfENT1 transporter. Dr. Akabas worked with two MSTP students in his lab (I.J. Frame and Roman Deniskin) as well as colleagues at Einstein (Drs. Ian Willis and Robyn Moir) and Columbia University (Drs. Donald Landry and David Fidock). The researchers used their technique to screen 64,560 different compounds. They identified 171 potential antimalarial drugs. Studies of nine of the most potent drugs showed that they kill P. falciparum parasites in laboratory culture.
"We've shown that the PfENT1 transporter is a potential drug target for developing novel antimalarial drugs," said Dr. Akabas, senior author of the ACS Chemical Biology paper and a professor of physiology & biophysics, of medicine and in the Dominick P. Purpura Department of Neuroscience at Einstein. "By using our rather simple approach, scientists could create similar high-throughput screens to identify inhibitors for killing other parasites that rely on transporters to import essential nutrients."
Last month, the National Institutes of Health awarded Dr. Akabas and his Columbia University collaborators a five-year, $3.45-million grant (1R01AI116665) to use his high-throughput assay to find and develop antimalarial drugs. Einstein has applied for patents to cover this assay.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2013-2014 academic year, Einstein is home to 743 M.D. students, 275 Ph.D. students, 103 students in the combined M.D./Ph.D. program, and 313 postdoctoral research fellows. The College of Medicine has more than 2,000 full-time faculty members located on the main campus and at its clinical affiliates. In 2013, Einstein received more than $150 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center - Einstein's founding hospital, and three other hospital systems in the Bronx, Brooklyn and on Long Island, Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook, and view us on YouTube.