Disrupting the cycle
Malaria infects around 250 million people each year and causes more than 600,000 deaths globally, according to the World Health Organization. While standard antimalarial drugs clear the parasite from the blood and resolve symptoms, they don’t necessarily stop transmission from one person to another via mosquitoes.
To stop the parasite spreading, Dr Sayers and her colleagues have zeroed in on specific proteins involved in the male parasite’s reproduction.
“If we disrupt these proteins in the male parasite – which effectively acts as the malaria parasite sperm – the cells can’t develop properly, so the parasite can’t be transmitted.”
The idea has already led to promising results in the lab. Dr Sayers has shown that disrupting these proteins does stop the parasite from reproducing in mosquitoes. But there’s still at least another decade of research in animal models and drug design before a treatment could be used to prevent malaria transmission to humans.
When this happens, the approach could be built into existing treatments for the symptoms of malaria delivered in drugs taken orally or by injection. This will have the dual function of clearing the infection and halting the spread of the parasite from one individual to another.
Beyond malaria
But in studying these proteins – which are produced by a gene involved in male parasite reproduction – Dr Sayers and her colleagues found they’re not unique to malaria parasites.
“I found this male-specific gene in the parasite’s sperm cells, and it’s present in pretty much all sexually reproducing species, including humans,” she says.
When she looked more closely, she found the human version is highly expressed in the testes – suggesting it may play a role in sperm development – raising the possibility that the parasite’s same biological machinery could also be at work in human sperm. So if tampering with the proteins can cause the male Plasmodium parasites to become infertile, maybe there’s something similar going on in the genes of infertile men.
“There are some published studies showing infertile men with mutations in these proteins or changes in the expression of these genes, so it’s not such a wild idea that there’s a link,” Dr Sayers says.
She takes the idea a step further with a more speculative line of inquiry: whether these same male sex genes could be targeted to develop a non-hormonal male contraceptive.
“I’m talking about malaria on one hand and male contraceptive pills on the other. It might sound like a strange leap to make, but the biology could be connected. Right now it’s an idea, but I think it’s definitely something worth exploring in future research.”