A Purdue researcher is taking a giant leap forward in the fight against drug-resistant strains of malaria in developing countries.
Open Philanthropy has awarded $1.38 million to Philip Low to further validate a drug therapy that he and his colleagues have previously shown to successfully treat the disease. Low (rhymes with “now”) is Purdue University’s Presidential Scholar for Drug Discovery and the Ralph C. Corley Distinguished Professor of Chemistry in the College of Science.
For years, experts have been concerned about the rise of drug-resistant malaria variants in Southeast Asia and the prospect that one or more of these strains might travel to Africa. A similar event occurred in the 1980s with the emergence of drug resistance to the then-standard treatment of chloroquine, which resulted in millions of deaths.
But Low is working to save lives on both continents by conducting clinical trials to validate previous results and to test whether the number of days of an anti-malaria treatment can be reduced.
While studying how malaria propagates in human blood, Low and his research team discovered that the cancer drug therapy imatinib is effective in the treatment of drug-resistant malaria. Trials in Southeast Asia showed that imatinib, when combined with the customary malaria therapy, clears all malaria parasites from 90% of patients within 48 hours and 100% of patients within three days. The patients receiving imatinib were also relieved of their fevers in less than half of the time experienced by similar patients treated with the standard therapy.
Open Philanthropy has awarded Low $600,000 for a larger clinical trial in Southeast Asia to validate his previous trials. The organization has also awarded Low $780,000 to determine whether the usual three-day therapy can be reduced to two days or even one. This work will be focused in the African countries of Kenya and Tanzania where malaria is prominent.
We found that people in Africa must often walk many miles to obtain treatment for malaria. They will receive three pills, walk all the way home, take one or two pills, start to feel better, and then save the third pill for their next malaria infection. When they don’t finish the course of treatment, only the most drug-resistant strains of the parasite survive and spread. And that’s how people build up drug resistance. So we’d like to eventually be able to cure all patients with just one pill. It would prevent these drug-resistant strains from ever proliferating.”
Philip Low, Purdue University
Open Philanthropy is a grantmaking organization whose mission is to use its resources to help others as much as it can, according to the funder.
“This is yet another case of an organization recognizing Philip Low’s brilliance, scientific vision and mission to help people in all corners of the world,” said Brooke Beier, senior vice president of Purdue Innovates. “The Purdue Research Foundation has been a proud partner in supporting his work, protecting and promoting his intellectual property that is changing lives and making our world a better place to live.”
Since 1988, Low has been listed on more than 145 invention disclosures to the Purdue Innovates Office of Technology Commercialization. He has been listed on more than 600 patents in nearly two dozen countries around the world from the U.S. Patent and Trademark Office and international patent organizations. During his tenure at Purdue, Low has been awarded 213 research grants for more than $43.5 million. His work also receives support from the Purdue Institute for Cancer Research and the Purdue Institute for Drug Discovery.
Imatinib was originally produced by Novartis for the treatment of chronic myelogenous leukemia and other cancers. It works by blocking specific enzymes involved in the growth of cancers.
“When we discovered the ability of imatinib to block parasite propagation in human blood cultures in petri dishes, we initiated a human clinical trial where we combined imatinib with the standard treatment (piperaquine plus dihydroartemisinin) used to treat malaria in much of the world,” Low said.
Malaria infects human red blood cells, where it reproduces and eventually activates a red blood cell enzyme that in turn triggers rupture of the cell and release of a form of the parasite called a merozoite into the bloodstream. Low and his colleagues theorized that by blocking the critical red blood cell enzyme, they could stop the infection. The data from initial drug trials have confirmed that.
“Because we’re targeting an enzyme that belongs to the red blood cell, the parasite can’t mutate to develop resistance -; it simply can’t mutate our proteins in our blood cells,” Low said. “This is a novel approach that will hopefully become a therapy that can’t be evaded by the parasite in the future. This would constitute an important contribution to human health.”
The goal, Low said, is to get this into developing countries to save lives. With this new round of funding, he says they’re now closer than they’ve ever been.