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PUBLIC RELEASE DATE:
20-Mar-2013

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Contact: Todd Murphy
murphyt@ohsu.edu
503-494-8231
Oregon Health & Science University
@ohsunews

Scientists develop drug that might be next best hope against malaria

Drug may be major advance as malaria has developed resistance to existing treatments

PORTLAND, Ore. - Scientists at Oregon Health & Science University and the Portland VA Medical Center have developed a drug that may represent one of the world's best hopes for treating and preventing malaria -- a disease that kills more than one million people each year.

The scientists have described the drug, and its effectiveness against mice infected with malaria, in the March 20 issue of Science Translational Medicine, an interdisciplinary journal of the American Association for the Advancement of Science.

The drug -- called ELQ-300 -- "is an exciting compound as it ticks a number of boxes necessary in a next-generation antimalarial," said Dr. Timothy Wells, the chief scientific officer for Medicines for Malaria Venture, a Swiss non-profit that is leading the scientific fight against malaria and that helped fund the research leading to ELQ-300. "It has potential to become part of a combination therapy that could cure patients, prevent infection and block the transmission of malaria -- all at low-doses -- which means fewer and smaller pills for patients, at a lower cost. Provided a formulation can be developed, ELQ-300 holds great promise to become a tool to help shrink the malaria map."

Malaria infects more than 200 million people per year and kills more than 1.2 million -- many of them children under 6 and many of them living in Africa.

The two main drugs that have been used to treat malaria over the last several decades -- quinine and chloroquine -- have become less effective as the parasite that causes malaria has become resistant to the drugs.

As described in Science Translational Medicine, ELQ-300 was extremely potent against malaria in mice. It also has another distinct advantage: it targets the parasite that causes malaria much earlier in the process than existing drugs do. Most of the drugs in clinical use today target a form of the parasite only after it has unloaded millions or even billions of "merozoites" into the human bloodstream. ELQ-300 targets the parasite earlier when it is in the liver, and when its numbers are much lower, before anything has spilled into the bloodstream.

That means the drug can be incredibly potent and may be able to not only treat malaria in a single dose, but also prevent malaria before any serious disease symptoms develop.

"We believe ELQ-300 has a chance to change the landscape of how we fight malaria across the world," said Michael Riscoe, Ph.D., principal investigator in the research, a professor of molecular microbiology and immunology at OHSU and director of the Experimental Chemotherapy Lab at the Portland VA Medical Center.

One distinct advantage of the drug could be its potency -- that it could treat malaria in a single dose. A major problem with existing malaria drugs is that they require multiple doses over a number of days to achieve a cure. If people miss a dose, that means the drug won't work, and it allows the parasite to develop resistance against the drug, Riscoe said.

With a drug that only requires a single dose, a medical professional or aid worker can observe a person taking the medicine to ensure compliance.

Any new anti-malarial drug also would become part of a drug "cocktail" and be used in combination with other drugs to prevent the emergence of resistance, Riscoe said.

Malaria is a major health problem in tropical areas. It accounts for 40 percent of all public health spending in Africa. It also presents a major disease hazard to travelers in the tropics and subtropics.

Malaria also can have long-term consequences even to people who aren't killed by the disease. For every death from malaria, there are many others -- children 6 and under especially -- who suffer long-term cognitive and other problems from the fever and a severe condition known as cerebral malaria.

While ELQ-300 was designed and synthesized by OHSU and Portland VA scientists, an international network of scientists has collaborated to extensively profile the drug. On the basis of those scientists' findings, ELQ-300 has been selected as a drug that Medicines for Malaria Venture will recommend for further studies in humans. Efforts are underway to define the formulation that would be used in human clinical trials.

Riscoe and other scientists who have been working on ELQ-300 hope the drug can be ready for initial human clinical trials within one to two years.

"Dr. Riscoe and his colleagues have been able to take this idea from its very basics to something that might be nearing clinical trials -- all with the support of MMV, the VA, and OHSU," said J. Timothy Stout, M.D., Ph.D., M.B.A., vice president for Technology Transfer and Business Development at OHSU. "We're extremely excited about what this could mean for the fight against a neglected disease that still ravages large parts of the world."

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Along with OHSU, the VA and Medicines for Malaria Venture, the National Institutes of Health (grant number AI100569) also supported this research.

About OHSU

Oregon Health & Science University is a nationally prominent research university and Oregon's only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children's Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university's social mission. OHSU's Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer's disease and new treatments for Parkinson's disease, multiple sclerosis and stroke. OHSU's Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.



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