COST Action B22 on

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COST Action B22 on Drug Development for
Parasitic Diseases

• The Problem
• African sleeping sickness
• about 500.000 fatalities / yr in Africa
• Chagas disease
• 18 million people infected in latin America and
  40.000 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.

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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

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COST Action B22 on Drug Development for
Parasitic Diseases (2002-2007)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)

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COST Action B22 on Drug Development for
Parasitic Diseases

• 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

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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

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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 2004 3 in 2005 and 1 in 2006
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COST Action B22 on Drug Development for
Parasitic Diseases
Annual meetings of COST Action B22 1st Annual
Congress, 22-24 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,
10-13 June, 2007, Dundee, Scotland.

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COST Action B22 on Drug Development for
Parasitic Diseases
Website www.icp.be/cost/costb22/
E-mail list Costb22_at_big.icp.ucl.be
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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
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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)
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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).

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