EU-funded researchers have discovered that drugs originally designed to inhibit the growth of cancer cells can also kill the parasite that causes malaria. They believe this discovery could open up a new strategy for combating this deadly disease, which infects 250 million and kills nearly 1 million people worldwide every year. Efforts to find a treatment have so far been marred by the parasite’s ability to quickly develop drug resistance. The research was published online in the journal Cellular Microbiology.
Scientists working in France and Switzerland showed that, in order to proliferate, the malaria parasite depends upon a signalling pathway present in the host's liver cells and in the red blood cells. They demonstrated that the parasite hijacks the kinases (enzymes) that are active in the signalling pathway to serve its own purposes. When the research team treated red blood cells infected with malaria with cancer chemotherapy drugs called kinase inhibitors, the parasite was stopped in its tracks.
Everything started when the scientists tested red blood cells infected with Plasmodium falciparum parasites and showed that the specific PAK—MEK signalling pathway was more highly activated in infected cells than in uninfected cells. When the pathway was disabled pharmacologically, the parasite was unable to proliferate and died. Applied in vitro, the drug also killed a rodent version of malaria (P. berghei). According to the researchers, this indicates that hijacking the host cell’s signalling pathway is most probably a generalised strategy used by malaria parasites, and thus, disabling that pathway would likely be an effective strategy in combating the different strains of malaria parasite that infect humans.
Until now the parasite has managed to avoid control by quickly developing drug resistance through mutations and hiding from the immune system inside liver and blood cells in the body of the host, where it proliferates. The discovery that the parasite needs to hijack a signalling pathway in the host cell opens up a whole new strategy for fighting the disease. ‘Instead of targeting the parasite itself, we could make the host cell environment useless to it,’ the scientists said. They added: 'Because this strategy uniquely targets cell enzymes in the host, the parasite will be deprived of a major modus operandi for development of drug resistance – namely a selection of mutations in the drug target.’
Several of these kinase—inhibiting chemotherapy drugs are already used clinically in cancer therapy, and many more have already passed stage one and stage two clinical trials. Even though these drugs have toxic side—effects, they are still being used over extended periods for cancer treatment. In the case of malaria, that would require a shorter treatment period, the problem of toxicity would be less acute. They suggest therefore that these drugs should be evaluated immediately for anti—malarial properties, drastically reducing the time and cost required to put this new malaria—fighting strategy into practice.
The study was funded in part by four EU projects: ANTIMAL ('Development of new drugs for the treatment of malaria); BIOMALPAR ('Biology and pathology of the malaria parasite'); MALSIG ('Signalling in life cycle stages of malaria parasites'); and EVIMALAR ('Towards the establishment of a permanent European virtual institute dedicated to malaria research').
Both ANTIMAL and BIOMALPAR were funded under the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6) to the tune of EUR 17.75 million and EUR 16 million respectively. Supported under the Health Theme of the Seventh Framework Programme (FP7), MALSIG and EVIMALAR have each received EUR 3 million and EUR 12 million in funding.
To restrict search results to articles in the Information Centre, i.e. this site, use this search box rather than the one at the top of the page.
After searching, you can expand the results to include the whole Research and Innovation web site, or another section of it, or all Europa, afterwards without searching again.
Please note that new content may take a few days to be indexed by the search engine and therefore to appear in the results.