Lastman Muthko lies at a Médecins Sans Frontières hospital in the Upper Nile in South Sudan in July.
A single anti-malarial pill with no side effects that blocks transmission of the killer disease could soon be available, University of Cape Town scientists announced this week.
Based on a recently discovered chemical compound, the cure could deal with many of the shortcomings that have prevented an effective treatment for the infectious disease that, according to the World Health Organisation, kills a child in Africa every minute.
Professor Kelly Chibale, project leader at the university’s Drug Discovery and Development Centre, said very low doses of the treatment had proved effective in animal tests. It was now ready for preclinical development and human clinical trials were expected to start next year.
“A new drug was needed because the treatments currently available have shortcomings that range from negative side effects to resistance and noncompliance,” he said. “Our compound has the potential to kill off a number of drug-resistant strains of malaria in Africa and Asia, as well as improve compliance, given the potential single-dose administration.”
Named the MMV390048 molecule, the compound was designed, synthesised and evaluated in a record 18 months in the centre’s laboratory from commercially available chemicals. The project entailed the collaboration of researchers from the Medicines for Malaria Venture in Switzerland, the Swiss Tropical and Public Health Institute and Monash University in Australia.
Science and Technology Minister Naledi Pandor praised it as an “African solution” in the global race to combat malaria that could save millions of lives in sub-Saharan Africa. Her department invested R25-million in the programme.
Chibale explained that the malaria parasites transmitted by female anopheles mosquitoes attack the liver and then invade the red blood cells, which is when symptoms such as fever manifest. Mosquitoes that feed on the infected blood then spread the disease.
Resistance
Most antimalarial treatments are aimed at controlling the disease once it has passed from the liver to the blood stream. The problem is that they require up to four daily doses of tablets, which is particularly problematic for poor people often also burdened with treatment regimes for HIV and tuberculosis.
“People often stop taking the malaria drugs when they start feeling better and this contributes to parasites developing resistance to the drugs. These are some of the reasons why we need a single oral dosage with no side effects,” Chibale said.
MMV390048 had proved effective against drug-resistant parasites and had shown the potential to block further transmission of the disease, he said. The animal tests had also shown no toxicity build-up or adverse side effects.
“A clinical fallout of Western medicines such as chloroquine is that malaria parasites have recognised they are under attack and have worked out ways to survive. One of our requirements will be to test MMV390048 on new parasite strains that emerge in the field, because this will influence in which parts of the world it will be released.”
According to the 2011 World Malaria Report, half the world’s population is at risk of catching the disease. Most of the 216-million cases and 655000 deaths recorded in 2010 occurred in sub-Saharan Africa, where the disease accounts for 24% of total child deaths.
Antimalarial potential
Chibale said his researchers had identified MMV390048 while looking for molecules that would kill the malaria parasites. It was part of the aminopyridine series of chemical compounds initially identified by Griffith University scientists in Australia as part of the Medicines for Malaria Venture’s malaria-screening campaign involving about six million compounds.
A team of scientists from the Drug Discovery and Development Centre further scrutinised and explored the antimalarial potential of the series and selected the most promising compounds for retesting.
“We knew by last September that MMV390048 offered a potential cure, but we had to compile a lot of data to show its safety and efficacy before we could announce it,” Chibale said. “Our scientific approach doesn’t require us to know how the molecule works, but rather to make sure that it does.”
An expert committee has cleared MMV390048 for testing on humans, which will probably start towards the end of next year after various formulations have been completed and candidates have been recruited. Although the sites for preclinical development had not been finalised, most would be based in South Africa, Chibale said.