KU Leuven researchers identify promising drug for treating severe malaria

Researchers at the Rega Institute – KU Leuven have reported promising results using ruxolitinib to treat severe malaria. The study, conducted in mice, shows that the drug prevents both inflammation and life-threatening hypoglycaemia, two disease processes that are often fatal in malaria patients.

Progress is being made in the fight against malaria. Suriname, for instance, was recently declared malaria-free by the World Health Organization (WHO), the first country in the Amazon region to achieve this. Nevertheless, malaria remains one of the world’s leading infectious diseases, with a particularly high death toll in Africa. Nearly 600,000 people die from the disease each year, most of them young children. 

The Laboratory of Immunoparasitology (Rega Institute – KU Leuven) is working to unravel the complexity of the disease. ‘Malaria occurs in varying degrees of severity: most people experience mild symptoms, while others develop severe complications. Fifteen to twenty percent of those severe cases are fatal,’ explains Professor Philippe Van den Steen, head of the laboratory. ‘These cases involve serious complications, including dangerously low blood sugar levels and elevated lactic acid levels, both of which can be life-threatening.’ 

Disrupted glucocorticoid function  

In their new study, published in EMBO Molecular Medicine, the researchers investigated why these complications occur and what role the stress hormones known as glucocorticoids play. In studies conducted on mice with malaria, disabling the action of glucocorticoids led to excessive sugar consumption in the liver and spleen. This resulted in life-threatening low blood sugar levels combined with extreme inflammatory responses.

‘In earlier research, we also found that the glucocorticoid function is impaired in certain malaria patients. The hormones are present, but they don’t function properly,’ says Professor Van den Steen. Glucocorticoids appear to play a crucial protective role in malaria. 

New use for existing medication

‘Further analysis showed that in cases of severe malaria in mice, there is increased activity in a specific molecular process known as the JAK/STAT pathway. We also found similar indications in patient data,’ says first author Fran Prenen, who dedicated her doctoral studies to this research. ‘We therefore tested ruxolitinib, a drug that inhibits this process and is already used to treat other diseases. Treatment with this drug prevented both the low blood sugar levels and inflammation, and saved the lives of the infected mice.’ This means that ruxolitinib may be promising as a potential treatment for severe malaria.

Further research  

Further research is needed to determine whether the promising results with ruxolitinib also apply to patients. ‘In our lab, we will continue to investigate the mechanisms underlying malaria and the severe complications that can occur in some cases,’ concludes Philippe Van den Steen. ‘It is possible that other existing medications may also affect the processes we have identified.  In addition, we aim to conduct patient studies to further clarify the link between the JAK/STAT pathway and severe malaria cases.’ 

This article was first published on 23 July by KU Leuven.