COST Action B22 on “Drug Development for Parasitic Diseases” The Problem African sleeping sickness: –about fatalities / yr in Africa Chagas’ disease: –18 million people infected in latin America and deaths / yr Leishmaniasis: –12 million people infected and 350 million people at risk in tropical and sub-tropical areas Malaria: –500 million cases world-wide and 2-3 million fatalities / yr Other parasitic diseases –Amaebiasis, giardiasis, trichomoniasis, cryptosporidiosis, etc. COST European Cooperation in the Field of Scientific and Technical Research

COST Action B22 on “Drug Development for Parasitic Diseases” The purpose of the action is to improve antiparasitic drug treatment by: Promoting collaboration between research laboratories Stimulating development and testing of new drugs Establishing a dialogue between scientists, public health workers and people from industry by organising scientific meetings and workshops

COST Action B22 on “Drug Development for Parasitic Diseases” ( ) The countries (21) Austria (1) Belgium (2) Bulgaria (1) Canada (1) Czech Republic (1) Denmark (1) France (2) Germany (2) Greece (2) Ireland (1) Associated members –Canada, IOCD, DNDi, Australia, SBRI, South Africa Israel (2) Italy (2) Lithuania (2) Luxemburg (1) Portugal (2) Slovakia (2) Spain (2) Sweden (2) Switzerland (2) The Netherlands (2) United Kindom (2)

Activities: Organisation of a general congress each year in one of the member countries Organisation of specialised workshops Short term missions between laboratories of member states COST Action B22 on “Drug Development for Parasitic Diseases”

Working groups: 1. Genetic approaches to validate potential drug targets 2. Drug-target evaluation (in vitro and in vivo) 3. Drug screening 4. Pre-clinical development 5. Drug resistance COST Action B22 on “Drug Development for Parasitic Diseases”

Publications (situation 30 November 2006): Well over 600 publications in peer reviewed journals Joint publications: 43 collaborative papers since the start of the Action. STSMs: 3 in in 2005 and 1 in 2006 COST Action B22 on “Drug Development for Parasitic Diseases”

Annual meetings of COST Action B22: 1st Annual Congress, November, 2004, Antwerp, Belgium. 150 participants 2nd Annual Congress, 29 Sept - 1 Oct, 2005, Siena, Italy. 155 participants 3rd annual Congress, 1-4 October, 2006, Athens, Greece. 175 participants 4th Annual Congress, June, 2007, Dundee, Scotland. COST Action B22 on “Drug Development for Parasitic Diseases”

Website: list: COST Action B22 on “Drug Development for Parasitic Diseases”

Results: Three genome projects of trypanosomatids completed (Science 15 July, 2005) Drug targets identified using RNAi techniques (several groups) Antitrypanosome diamidines in clinical trials (Brun, Basel) Antimalarial phospholipid (Henri Vial, Montpellier) and internal peroxide derivatives (Bernard Meunier) in clinical trials COST Action B22 on “Drug Development for Parasitic Diseases”

Some highlights Drug target validation using novel RNAi techniques: Cyclic AMP-specific phosphodiesterases in T. brucei (T. Seebeck, Bern) New antimalarial lead compounds: Phospholipid analogues (Henri Vial, University of Montpellier, France in collaboration with Sanofi-Aventis)

Thomas Seebeck, Bern Two cAMP-specific phosphodiesterases of T. brucei are absolutely essential. If RNAi is induced against them either in culture or in the mouse, the cells are killed, and the infection is eliminated. This system mimicks quite nicely the effect of phosphodiesterase inhibitors, and certainly defines the PDEs as good targets. PDEs are well-studied targets in human pharmacology, and so a lot of expertise is available in the pharma industry on how to screen and develop PDE inhibitors. FASEB Journal (in press).

Phospholipd metabolism as a drug target in Plasmodium merozoites Henri Vial, University of Montpellier, France