Antimalarial candidate holds promise as a single dose
By Laura Owings
In an article published last month (26 April) in the journal of Science Translational Medicine, researchers indicated that the compound MMV390048 could block all life cycle stages of the malaria parasite. It was also shown to be effective against resistant strains, prevent infection and block transmission.
“This drug profile reveals the potential to be part of a single-dose cure, benefitting people who are infected with malaria, and working as a preventative measure,” says Kelly Chibale, a corresponding author of the article and founding director of the University of Cape Town (UCT) Drug Discovery and Development Centre, H3D.
“This drug profile reveals the potential to be part of a single-dose cure, benefitting people who are infected with malaria.”
Kelly Chibale, University of Cape Town (UCT)
An estimated 212 million cases of malaria were identified worldwide in 2015, according to WHO. Over 90 per cent of those were in Africa.
MMV390048 is a derivative small molecule belonging to the aminopyridine class. It was first announced as a preclinical development candidate in 2012, and in 2014, it was the first new anti-malarial candidate to enter phase I human studies in Africa when clinical trials began at the UCT Clinical Research Centre. Those clinical trials ended in 2015, but the data has not yet been published, Chibale explains.
This article provides preclinical data demonstrating the potential of the compound for the treatment, prophylaxis and cure of malaria in mice and monkey models. The trials involved administering MMV390048 to mice and monkeys before and after infection.
Done as a precursor to clinical studies, Chibale says this research provided a guideline for therapeutic dosage levels that would apply to human models, and gave confidence that the drug could indeed work in humans.
The article shows the drug’s efficacy across the three stages of the parasite’s life cycle: liver, blood and transmission. According to Chibale, this means the drug could kill the parasite in infected individuals before symptoms present, but could also be used when patients are visibly ill, and help block further mosquito transmission.
The drug is set to enter the second phase of clinical trials in 2017 in Ethiopia. If the outcomes of these trials are successful and funding is available, Chibale says the drug could be on the market in six to eight years.
Maureen Coetzee, director of the Wits Research Institute for Malaria at the University of the Witwatersrand in South Africa, tells SciDev.Net that if the drug becomes available on the market, it would be a noteworthy advance, but adds that measures to control mosquitoes are also needed.
“Finding and treating those people [carrying the parasite] is an immense task, and as long as the malaria vector — mosquitoes — are around, they will feed on those people and transmit the parasites to new hosts,” she says.
Tanya Paquet and others Malaria antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase (Science Translational Medicine, 26 April 2017)