Researchers discover single-dose malaria drug
Effective against the most deadly forms of the malaria parasite as well as drug-resistant types
Novartis and collaborators have discovered a drug candidate that shows promise as a next-generation treatment for malaria after mice were cured of the disease with a single dose.
Scientists at the Novartis Institute for Tropical Diseases (NITD), with researchers from the Genomics Institute of the Novartis Research Foundation (GNF), the Swiss Tropical and Public Health Institute and The Scripps Research Institute, say the anti-malarial candidate, spiroindolone NITD609, is effective against the two most common strains of the malaria parasite, Plasmodium falciparum, the most deadly form, and Plasmodium vivax. It is also effective against a number of drug-resistant strains.
Bryan Yeung from Novartis Institute of Tropical Diseases, who led the project, said they identified NITD609 by screening the Novartis archive of 12,000 pure natural products and synthetic compounds active against P. falciparum.
The first screen turned up 275 compounds, which was narrowed to 17 potential candidates that displayed the desired physicochemical properties for drug development, as well as a mechanism of action distinct from the currently used anti-malaria therapies that are based on aminoquinolines and artemisinin derivatives.
Unlike existing antimalarial drugs, NITD609 works by rapidly suppressing protein synthesis in the parasite. The team discovered its target by screening the drug candidate against a panel of parasite strains with defined genetic mutations. Strains with mutations in a protein called PfATP4 were resistant to its effects, indicating that this protein is important for NITD609 to work.
The research findings were reported in the journal Science.
According to the World Health Organization (WHO), in 2008 there were more than 240 million cases of malaria, causing nearly one million deaths, mostly among young children in Africa.
‘Malaria remains a scourge,’ said Mark Fishman, president, Novartis Institutes for BioMedical Research.
‘The parasite has demonstrated a frustrating ability to outwit new medicines, from quinine to today's unsettling increased tolerance to artemisinin derivatives. We are delighted that our scientists could provide this potential new malaria therapy, based on an unprecedented chemical structure and directed to a novel target.’
Rick Davis, business development manager at the Wellcome Trust, added: ‘A single dose cure would go a long way to addressing the unmet medical need in malaria, and we look forward to seeing how this compound performs in clinical trials.’
Further safety evaluation is currently ongoing and, provided the outcome of these studies is favourable, a phase I clinical trial in humans could begin at the end of the year.
Major support for the project was provided by the Wellcome Trust, the Medicines for Malaria Venture (MMV) and A*STAR, as well as the US and Singapore governments.