New malaria drug clears parasite, prevents transmission, study finds
A drug that both cures malaria and prevents the transmission of the deadly disease may be one step closer, research suggests.
Scientists found inhibiting the protein PfCLK3 blocks several stages that are critical to the complex life cycle of the parasite behind the killer illness.
Tests showed it prevented the parasite inside mice from developing into the “mature phase” that infects humans through mosquitoes.
One expert called the study by researchers at the University of Glasgow “exciting”. But they added multiple approaches are needed to combat treatment resistance, with “no one drug being able to eradicate malaria”.
Earlier this week, the World Health Organisation (WHO) warned malaria will not be wiped out in the near future with “the tools we have today”.
More than 200million cases occur every year worldwide, causing around 500,000 deaths, the researchers wrote in the journal Science.
Attempts to control outbreaks have been hindered by the parasites’ slowly growing resistance to drugs.
There is, therefore, an “urgent need for novel strategies to cure malaria while also preventing transmission”.
To edge closer to this, the researchers screened more than 24,000 compounds that are thought to be involved in a malaria parasite’s development.
They focused on Plasmodium falciparum, which is the most common species worldwide and the most likely to be fatal.
PfCLK3 was identified as having a ‘central role’ in regulating the parasite’s gene expression. To put this to the test, mice were infected with Plasmodium falciparum. The researchers then blocked PfCLK3 within the parasites in the rodents.
This suppressed the activity of more than 400 genes that are “essential” to the pathogen’s survival.
In turn, this prevented the pathogen from multiplying in the animals’ red blood cells. Eventually, these cells burst, which causes a sufferer to experience the tell-tale malaria fever.
Blocking PfCLK3 also prevented other forms of the parasite from circulating in the mice’s blood.
When a mosquito bites an infected human, it ingests these parasites. These then make their way to the insect’s salivary glands, enabling it to infect others.
Overall, inhibiting PfCLK3 “was highly effective at clearing rodent malaria parasites from infected mice”.
The approach also led to “anti-parasite activity” against the malaria species Plasmodium berghei, which infects certain rodents, and knowlesi, which largely affects macaque monkeys.
This suggests blocking PfCLK3 could work across “multiple malaria species”.
However, the researchers note the same approach may not be effective in humans.
Dr. Jake Baum, professor of cell biology and infectious diseases at Imperial College London, said: “We stand at a key cross-roads in malaria control and eradication. There is rising drug resistance in south east Asia and we have stalled in our efforts to reduce malaria incidence globally.
“As such, there is an urgent need, just like with antibiotic resistance, to find new drugs with new modes of action. This is where the current study fits in, looking at an exciting class of drugs that indeed works in a new way.”
He added: “So far, in this paper, the authors show the drug has robust activity, targeting the malaria parasite at several stages in its lifecycle.
“It is still very early in development and there’s a long way to go before these drugs would even be put into testing in humans, but we need a full pipeline for the long road if we are to achieve global eradication.”
Baum added, however, “no one drug will eradicate malaria”. He said: “We need not just a replacement but a pipeline of replacements. It’ll always be a revolving door – new drugs in, old ones out as nature always finds a way to evolve resistance. We should be clear, no drug alone will eradicate malaria.”
The WHO warned last week it is not yet possible to put a date on when malaria may be eradicated.
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