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 1.5–2 million new cases of
leishmaniasis and 80,000 deaths each year, and 350 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.
