A drug already in use to treat malaria and certain autoimmune diseases in pregnant women has shown promise in reducing transmission of Zika virus from mothers to their foetuses, according to a new study led by an Indian-origin researcher.
The drug, Hydroxychloroquine, works by inhibiting autophagy, a process by which cells remove toxins and recycle damaged components to generate energy. Researchers showed that Zika virus may manipulate this process in the placenta to infect the developing foetus.
In a study published online in the Journal of Experimental Medicine, the researchers, led by Indira Mysorekar from Washington University School of Medicine in St. Louis, showed how the drug appeared to reduce transmission of Zika virus from pregnant mice to their foetuses.
“Zika virus infection during pregnancy can lead to a devastating array of birth defects, including microcephaly, abnormal reflexes, epilepsy, and problems with vision, hearing and digestion,” said Catherine Spong, Deputy director of US National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which funded the work.
“This study suggests that treating Zika-infected pregnancies with autophagy-inhibiting drugs may lower the risk of these abnormalities, but more research is needed to confirm these findings,” Spong added.
Previous research had established that autophagy plays an important role in the placenta’s defence against bacteria and other disease-causing agents.
In the current study, the researchers demonstrated that Zika virus infection activates autophagy in lab cultures of human placental cells and in the placentas of mouse models of Zika virus transmission.
The researchers administered hydroxychloroquine, a US Food and Drug Administration (FDA)-approved drug known to inhibit autophagy, to Zika-infected pregnant mice.
Mice treated with hydroxychloroquine have lower levels of detectable virus in their placentas and less placental damage, compared to untreated mice, the findings showed.
The treatment also restricted Zika infection in the foetal head and led to a larger foetal body size, suggesting that the drug limits cross-placental transmission of the virus.