Breach in drug resistance

New synthetic compound works differently on malaria

 
By Sugandh Juneja
Last Updated: Saturday 04 July 2015 | 02:50:09 AM

imageMALARIAL parasites are known to develop quick resistance to drugs. Two groups of scientists, working independently on alternative drugs for malaria, have identified a couple of compounds that could treat drug-resistant malaria.

One team synthesised and evaluated a compound called spiroindolone NITD 609. It is effective against drug resistant strains of two malaria parasites— Plasmodium falciparum and P vivax. The scientists from the Scripps Research Institute in USA and Swiss Tropical Institute in Switzerland, in collaboration with pharma company Novartis, screened 12,000 synthetic and plant-based compounds known to be active against P falciparum.

They selected 17 compounds confirmed to have effect on multi-drug resistant strains of the parasites. They chose spiroindolone first. “It has favourable physical and chemical properties for drug development as well as a mechanism of action distinct from the currently used therapies, including aminoquinolines, artemisinin derivatives or antifolates,” said Elizabeth Winzeler of Scripps Research Institute who led the research.

Next, the researchers tested the effect of the compound ex vivo on P falciparum and P vivax, isolated from patients on the Thai-Burmese border who had reported resistance to chloroquine. They found it effective. “NITD 609 rapidly cleared plasmodium in a malaria mouse model and showed pharmacological properties compatible with a once-daily dosing regimen,” said Thierry Diagana, co-researcher from Novartis Institute for Tropical Diseases in Singapore.

Spiroindolone works differently from other malarial drugs by inhibiting protein synthesis in the parasite which prevents its binding with the host cell. It showed no significant toxicity to host cells, implying it is safe. The researchers tested the compound on a multi-drug resistant strain with high tendency to mutate and found drug resistance was very low and did not increase. The results were published in the September 3 issue of Science. The compound could progress to clinical trials later this year.

Another group of scientists reported a derivative of artemisinin— arterolane—as an effective antimalarial drug. Their study was published in the September 15 issue of Clinical Infectious Diseases. The researchers from India and other countries in Asia, Africa and Europe, in collaboration with Indian Pharma company Ranbaxy Laboratories, tested on the drug in 2006.

The trials were conducted on 230 patients from Thailand, India and Tanzania, suffering from falciparum malaria. They checked arterolane’s efficacy by measuring time taken to clear the parasite from the blood. A 100 mg dose took 12.8 hours and a 200 mg dose took 12.6 hours to clear the parasites.

The rate of reappearance of disease varied between 28 per cent and 37 per cent. The research ran into controversy in 2007 when Medicine for Malaria (MMV), a non-profit in Switzerland, withdrew financial support to it, saying results were unsatisfactory. “MMV has now realised the potential of the drug and is supporting the development of the product,” said Neena Valecha of India’s National Institute of Malaria Research and lead author of the study.

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