Topical Drug Treatment of Cutaneous Leishmaniasis

Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis a disease that is characterized by a spectrum of clinical manifestations ranging from ulcerative skin lesions to fatal visceral infections Leishmaniasis is a poverty related disease and is associated with malnutrition displacement poor housing illiteracy gender discrimination weakness of the immune system and lack of resources Leishmaniasis is further compromised by the emergence of co infection with human immunodeficiency virus HIV in endemic areas Globally there are an estimated million new cases of leishmaniasis and deaths each year and million people are at risk of infection and disease In the absence of vaccination chemotherapy together with vector control remains one of the most important elements in the control of leishmaniasis However this strategy is seriously threatened by the high toxicity of clinical drugs and the rampant increase of resistance in the field As leishmaniasis is a disease of poverty pharmaceutical companies have had limited incentive for the search of novel anti leishmanial drugs because there would be low economic return on their investment The goal of this SBIR application is to develop an affordable and effective antileishmanial ointment for treating cutaneous leishmaniasis CL in both developed and developing areas of the world Our team recently discovered that zinc II dipicolylamine ZnDPA complexes have strong antileishmanial activity against Leishmania major one of the causative agents of CL Molecular Targeting Technologies Inc will develop ointment formulations of ZnDPA and the team at the University of Notre Dame will test these ointments in an in vivo model of CL that takes advantage of a genetically modified L major strain which stably express a red fluorescent mCherry protein Furthermore the proposed studies on skin toxicity and biodistribution of ZnDPA will be significant for a successful clinical translation Leishmania spp are parasitic protozoa responsible for a spectrum of diseases known as leishmaniasis Leishmaniasis represents a major international health problem has a high morbidity and mortality rate and is classified as an emerging and uncontrolled disease by the World Health Organization WHO There are few drugs available for the treatment of these diseases and most are expensive and highly toxic This project will apply new technology to test new compounds that can be developed into real solutions for the control of leishmaniasis