Novel application for an old drug: tamoxifen in the treatment of Leishmania infection
Leishmaniasis is an antropozoonotic disease with a wide range of clinical manifestations. In humans, signs of disease vary from skin and mucosal ulcers to enlargement of internal organs such as the liver and spleen. The unicellular parasite Leishmania amazonensis is able to infect humans and cause localized or diffuse skin lesions. The treatment for this disease is difficult, as it requires prolonged and painful applications of toxic drugs that are poorly tolerated. Therefore, a key area in leishmaniasis research is the study of new therapeutic schemes and less toxic drugs.
Researchers from the University of Sao Paulo, Brazil, have shown the efficacy of tamoxifen against L. amazonensis, one of the species that causes cutaneous leishmaniasis in South America. The paper explains how tamoxifen, a medication widely used in the treatment and prevention of breast cancer, fights the parasitic disease in experimentally infected mice. Unicellular parasites of Leishmania genus are the causative agents of leishmaniasis. Treatment of leishmaniasis requires the administration of toxic and poorly tolerated drugs. Having previously demonstrated that tamoxifen was active against parasites in vitro, the authors now show its efficacy in a rodent model of infection with L. amazonensis. The Brazilian group observed that infected mice treated with tamoxifen for two weeks showed a significant reduction in parasite burden. Researchers also detected a notable delay in the development of skin ulcers, a typical symptom of the disease caused by L. amazonensis. The promising results presented in this study, coupled with the fact that tamoxifen’s safety and pharmacological profiles in humans are well established (the compound that has been in clinical use since the 1970s for the treatment of breast cancer), point to a new alternative in the treatment of leishmaniasis. Further trials will be necessary in other experimental models of infection before the drug is tested in humans.
Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice. PLoS Negl Trop Dis 2008 2(6): e249
Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America. Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.
Tags: Biology, Health, Medicine, Microbiology, Parasitology, Science
