New drug target for developing cures for Kala-azar
doi:10.1038/nindia.2017.42 Published online 27 March 2017
Researchers have identified a drug target that could be exploited to develop new therapies for treating the parasitic disease, visceral leishmaniasis, in the Indian subcontinent1.
Commonly known as Kala-azar, visceral leishmaniasis is caused by Leishmania donovani, a parasite which is transmitted to humans through sandfly bites. Miltefosine is an orally administered drug that kills this parasite by increasing the levels of an enzyme known as methionine aminopepditase 2 (MAP2). However, roles of MAP2 in parasites’ death remain largely unknown.
To investigate the roles of MAP2, scientists led by Vikash Kumar Dubey, from Indian Institute of Technology Guhawati, Assam examined the biochemical effect of TNP-470, a well-known MAP2 inhibitor, on the miltefosine-induced controlled death of Leishmania parasites.
Although a combination of miltefosine and TNP-470 stopped the activity of specific killer enzymes, they increased the parasites’ death.
TNP-470 prevented miltefosine-induced membrane damage and DNA fragmentation by blocking the activity of MAP2. Since membrane damage and DNA fragmentation are signs of controlled cell death, these results suggest that MAP2, when not inhibited, could play vital roles in causing controlled death of the parasites.
These biochemical pathways and molecules, particularly MAP2 are very significant targets for developing novel drugs for visceral leishmaniasis.
“As Leishmania parasites constantly develop resistance to existing drugs, MAP2 inhibitor is a promising candidate to be used in combination with other drugs to kill drug-resistant parasites”, says lead author Ritesh Kumar from the IIT Guwahati, Assam.
1. Kumar, R. et al. Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani. Sci. Rep. 7, 95 (2017)