PARTNER 6

Short name: LSHTM

Principal Investigators: Dr. Simon Croft, Dr. Vanessa Yardley, London School of Hygiene & Tropical Medicine

Description: The Dept. of Infectious and Tropical Diseases has long experience and played a leading role in research on chemotherapy, immunology, taxonomy and epidemiology of leishmaniasis. Drug Discovery Group carries out research on chemotherapy of parasitic diseases, specifically leishmaniases, trypanosomiases and malaria and has a full range of animal models and a renovated state-of-the art rodent facility to be opened in April 2008. The group has long-standing links with organisations in the academia and pharmaceutical field.

Main tasks: Research: LSHTM will work closely with partners in the screening and evaluation of compounds in in vitro and in vivo models of infection. This will be based upon the long expertise of the group not just in the methodologies involved but also in the analysis of data, interaction with chemists and understanding of the drug development process, pharmacokinetics and formulations. Co-ordination: LSHTM will support the consortium management through establishment of a data base and system to enable all partners to have real-time access to updated efficacy data to guide decision making.

Previous experience: Expertise ranges from drug screening and evaluation in in vitro and in vivo models to resistance, combination studies, pharmaceutical formulations and immunomodulators. The LSHTM has extensive experience working with category 3 pathogens. Teams at the LSHTM have developed rodent models for research on the immunology and chemotherapy, with a range of parameters, of visceral and cutaneous leishmaniasis. LSHTM has been involved in setting up the TDR/WHO funded drug screening network, and been involved in training and technology transfer with groups in India and Africa. LSHTM is involved with organising in-house teaching programmes and hosting visitors to laboratories.

Simon L. Croft, PhD, is the Principal Investigator for LSHTM. He will coordinate LSHTM activities for the project consortium. Simon Croft draws on over 25 years of experience in the discovery and development of new drugs and formulations for the treatment of leishmaniasis, malaria, human African trypanosomiasis and South American trypanosomiasis. He gained a PhD at the Liverpool School of Tropical Medicine and expertise and experience on anti-parasitic chemotherapy while working with the Wellcome Research Laboratories, Beckenham, UK in the 1980s. His subsequent research while at LSHTM includes projects on miltefosine, AmBisome™ and topical paromomycin, all of which reached patients for leishmaniasis. Simon Croft was DNDi Research & Development Director between July 2004 and August 2007.

Vanessa Yardley, PhD, is a research fellow at LSHTM and was a manager of the LSHTM Drug Discovery group. For the last four years, Dr. Yardley has been the principal coordinator for the integrated anti-protozoal drug screen project (Leishmania spp., T.cruzi, T. brucei spp., Plasmodium spp. and Schistosoma spp.) funded by TDR/WHO and liaised with collaborators in academia and industry, analysing and reporting results. Prior to this project, Dr. Yardley was a research fellow for the ‘Molecular tools for monitoring emergence and spreading of drug resistance among natural populations of Leishmania’, an EC-funded project. She liaised with partners in Belgium, Peru and Bolivia to establish standard procedures for all aspects of the study and carried out biological assays to detect in vitro antimonial resistance from isolates.

Selected Publications:

1. Yardley, V., et al., American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug susceptibility? J Infect Dis, 2006. 194(8): p. 1168-75.

2. Rijal, S., et al., Antimonial treatment of visceral leishmaniasis:are current in vitro susceptibility assays adequate fro prognosis of in vivo outcome? Microbes Infect, 2006. in press.

3. Yardley, V., et al., The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine. Am J Trop Med Hyg, 2005. 73(2): p. 272-275.

4. Croft, S.L. and V. Yardley, Chemotherapy of Leishmaniasis. Curr Pharm Des, 2002. 8(4): p. 319-342.

5. Yardley, V. and S.L. Croft, Animal models of cutaneous leishmaniasis, in Handbook of Animal Models of Infection, O. Zak, Editor. 1999, Academic Press: London. p. 775-81.