Ahead of World Malaria Day (25 April), 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, according to World Health Organization statistics, infected around 225 million and killed nearly 800 000 people worldwide in 2009.
Efforts to find a treatment have so far been hampered by the parasite’s ability to quickly develop drug resistance. The research involved four projects funded by the EU (ANTIMAL, BIOMALPAR, MALSIG and EVIMALAR) and was led by laboratories in the UK, France and Switzerland with partners from Belgium, Germany, Denmark, Greece, Spain, Italy, Netherlands, Portugal, and Sweden, along with many developing nations severely affected by malaria.
“This discovery could lead to an effective anti-malaria treatment that would save millions of lives and transform countless others. This demonstrates yet again the added value both of EU-funded research and innovation in general and of collaboration with researchers in developing countries in particular. The ultimate goal is the complete eradication of the global scourge of malaria and collaborative work across many borders is the only way of confronting such global challenges effectively,” said Research, Innovation and Science Commissioner Máire Geoghegan-Quinn.
Cancer drugs to kill malaria parasite
Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites reproduce in the liver, and then infect and multiply in red blood cells. Joint research led by EU-funded laboratories at the Inserm-EPFL Joint Laboratory, Lausanne, (Switzerland/France), Wellcome Trust Centre for Molecular parasitology, University of Glasgow (Scotland), and Bern University (Switzerland) showed that, in order to proliferate, the malaria parasite depends upon a signalling pathway present in the host’s liver cells and in red blood cells. They demonstrated that the parasite hijacks the kinases (enzymes) that are active in human cells, to serve its own purposes. When the research team used cancer chemotherapy drugs called kinase inhibitors to treat red blood cells infected with malaria , the parasite was stopped in its tracks.
Until now the malaria parasite has managed to avoid control by rapidly developing drug resistance through mutations and hiding from the immune system inside liver and red blood cells in the body of the host, where it proliferates. The discovery that the parasite needs to hijack some enzymes from the cell it lives in opens up a whole new strategy for fighting the disease. Instead of targeting the parasite itself, the idea is to make the host cell environment useless to it, by blocking the kinases in the cell. This strategy deprives the parasite of a major modus operandi for development of drug resistance.
Several kinase-inhibiting chemotherapy drugs are already used clinically in cancer therapy, and many more have already passed phase-I and phase II 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, which would require a shorter treatment period, the problem of toxicity would be less acute. Researchers are proposing 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 next steps will include mobilising public and industrial partners to verify the efficacy of kinase inhibitors in malaria patients and to adjust the dose through clinical trials, before the new treatments can be authorised and made available to malaria patients worldwide.
Since 2002, the EU has invested nearly EUR 180 million in malaria research through the EU’s Framework Programmes for Research (FP6, 2002-2006, and FP7, 2007-2013).
The EU also contributes to the European and Developing Countries Clinical Trials Partnership (EDCTP) which aims to accelerate the development of new or improved drugs, vaccines and microbicides against HIV/AIDS, malaria and tuberculosis. Established in 2003, this successful ongoing European and African collaboration focuses on clinical trials as well as capacity building in sub-Saharan Africa. To date, 10 clinical trials on malaria costing EUR 69 million have been financed under EDCTP with EUR 35 million support from the EU.