Kinetoplastida: new therapeutic strategies.
New formulations and therapeutic switching of the established drugs, amphotericin B and paromomycin, together with the discovery of miltefosine, have significantly improved the opportunities for treatment of visceral leishmaniasis (VL) chemotherapy. However, for human African trypanosomiasis (HAT), Chagas disease and cutaneous leishmaniases there has been limited progress. For HAT, a novel diamidine, parfuramidine, is in phase III clinical trial for early-stage disease, but for the treatment of late-stage disease there are no new drugs and combinations of eflornithine with melarsoprol or nifurtimox have been the focus of clinical studies. For Chagas disease, different classes of compounds that have validated biochemical targets, sterol biosynthesis methylases and cysteine proteases, are in various stages of development. The genome sequences that are now available for the pathogens that cause the leishmaniases and trypanosomiases, and new methods for rapid validation of targets, are part of the solution to discover new drugs. The integration of medicinal chemistry, pharmacokinetics, project planning and interaction with the pharma/biotech sector are essential if progress is to be made. Although there are financial constraints, the appearance of new funding sources and not-for-profit product development partnerships offers hope for drug development.
Croft
S L
SL
Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK. simon.croft@lshtm.ac.uk
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004351:Drug Resistance; D004358:Drug Therapy / Q000639:trends; D004359:Drug Therapy, Combination; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy* / Q000517:prevention & control; D016896:Treatment Outcome; D014352:Trypanosomiasis / Q000188:drug therapy* / Q000517:prevention & control
D000981:Antiprotozoal Agents