Novartis/NIH-sponsored research yields promising malaria drug candidate
A chemical that rid mice of malaria-causing parasites after a single oral dose may eventually become a new malaria drug if further tests in animals and people uphold the promise of early findings.
- (1888PressRelease) September 06, 2010 - The compound, NITD609, was developed by an international team of researchers including Elizabeth Winzeler, a grantee of the National Institute of Allergy and Infectious Diseases, part of the USA’s National Institutes of Health and Swiss drug major Novartis (NOVN.VX).
The experimental drug NITD609 belongs to a new class of drugs called spiroindolenes. It was identified by the Novartis Institute for Tropical Diseases (NITD) working in an international collaboration supported by the Wellcome Trust, the international Medicines for Malaria Venture, the NIH and several other bodies.
"Although significant progress has been made in controlling malaria, the disease still kills nearly 1 million people every year, mostly infants and young children," says NIAID Director Anthony Fauci, noting: "It has been more than a decade since the last new class of antimalarials - artemisinins - began to be widely used throughout the world. The rise of drug-resistant malaria parasites further underscores the need for novel malaria therapies."
Compound has desirable features
Dr Fauci added: "The compound developed and tested by Dr Winzeler and her colleagues appears to target a parasite protein not attacked by any existing malaria drug, and has several other desirable features. This research is also a notable example of successful collaboration between government-supported scientists and private sector researchers."
The study, published in the September 3 issue of Science, was led by Thierry Diagana of the NITD and Dr Winzeler, who is affiliated with The Scripps Research Institute and the Genomic Institute of the Novartis Research Foundation, La Jolla, California.
Work on what eventually became NITD609 began in Dr Winzeler's lab in 2007. Scientists screened 12,000 chemicals using an ultra-high throughput robotic screening technique customized to detect compounds active against Plasmodium falciparum, the most deadly malaria parasite. The screen identified a chemical with good parasite-killing abilities and the potential to be modified into a drug. Medicinal chemists at the NITD then synthesized and evaluated about 200 versions of the original compound to arrive at NITD609, which could be formulated as a tablet and manufactured in large quantities. NITD609 is one of a new class of chemicals, the spiroindolones, which have been described in recently published research by Dr Winzeler and colleagues as having potent effects against two kinds of malaria parasites.
In the current study, the scientists detail attributes of NITD609 that suggest it could be a good malaria drug. For example:
* In test-tube experiments, NITD609 killed two species of parasites in their blood-stage form and also was effective against drug-resistant strains. In humans, malaria parasites spend part of their life cycle in the blood and part in the liver.
* The compound worked faster than some older malaria drugs, although not as quickly as the best current malaria drug, artemisinin.
* Other laboratory tests showed that NITD609 is not toxic to a variety of human cells.
GSK expects to seek Mosquirix approval by 2012
Also developing a novel treatment is UK drug giant GlaxoSmithKline (GSK. L), which is carrying out late-stage testing in people of an experimental vaccine against malaria and expects to see results by 2011. The firm says that, if it proves effective, it will seek regulatory approval for the vaccine, called Mosquirix, by 2012.
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