Repurposing Drugs to Combat Drug Resistance in Leprosy: A Review of Opportunities.
Leprosy is caused by extremely slow-growing and uncultivated mycobacterial pathogens, namely Mycobacterium leprae and M. lepromatosis. Nearly 95% of the new cases of leprosy recorded globally are found in India, Brazil, and 20 other priority countries [WHO, 2019], of which nearly two-thirds of the cases are reported in India alone. Currently, leprosy is treated with dapsone, rifampicin, and clofazimine, also known as multi-drug therapy [MDT], as per the recommendations of WHO since 1981. Still, the number of new leprosy cases recorded globally has remained constant in the last one-decade ,and resistance to multiple drugs has been documented in various parts of the world, even though relapses are rare in patients treated with MDT. Antimicrobial resistance testing against M. leprae or the evaluation of the anti-leprosy activity of new drugs remains a challenge as leprosy bacilli do not grow in vitro. Besides, developing a new drug against leprosy through the conventional drug development process is not economically attractive or viable for pharma companies. Therefore, a promising alternative is the repurposing of existing drugs/approved medications or their derivatives for assessing their anti-leprosy potential. It is an efficient method to identify novel medicinal and therapeutic properties of approved drug molecules. Any combinatorial chemotherapy that combines these repurposed drugs with the existing first-line [MDT] and second-line drugs could improve the bactericidal and synergistic effects against these notorious bacteria and can help in achieving the much-cherished goal of "leprosy-free world". This review highlights novel opportunities for drug repurposing to combat resistance to current therapeutic approaches.