COST Action B22 on
"Drug development for parasitic diseases"
2003-2007
Scientific Programme
The Scientific programme will be built upon:
1: Expert Working Groups and Meetings that address specific stages of the drug identification and development process
3: Scientific exchanges between laboratories
4: Support for scientific research
1: Expert Working Groups and Expert Meetings
A major activity in the proposed COST Action will be the expert meetings that focus on specific aspects of drug development. These include new drug targets, new tools for target discovery, validation or structural characterisation, and processes for biological pharmacological or toxicological characterisation of compounds. Consultants with relevant expertise outside parasitology will be invited to participate in the workshops, as well as representatives from European pharmaceutical companies and the Public Sector. Topics from the following areas will be considered by the Management Committee:
Drug Target Identification (Working Group 1)
The possibility and speed of identification of new drug targets has been changed dramatically by genomic analysis and the developing area of proteomics. As the sequencing of genomes of parasites will be completed within the next 5 years a large number of differences between parasites and host metabolism will emerge. These differences do not necessarily indicate essential genes/proteins and a combination of proteomics, microassays and molecular transfection methodologies will be required to validate potential drug targets. These genes must also be expressed during the infective stage of the parasites life cycle. This will involve studies in both tissue culture and animal models. The selection of a valid target at this point is important because of the significant commitment of resources involved in moving from a target to a lead compound. Expert Meetings/Workshops will focus on how new methodologies can be used to identify and validate relevant drug targets.Target Characterisation and Inhibitor Design (Working Group 2)
Novel drug targets will be characterised structurally and kinetically by NMR, X-ray crystallography and biochemical methodologies. This characterisation will lead directly to the rational design or high throughput screening of specific inhibitors/antagonists of the parasite target. Where crystals of the target protein are available, co-crystallisation studies will be used to reveal how the inhibitor is bound in the active site. This information can be used to generate a new pharmacophore, or virtual drug molecule, to direct more rational chemistry. Expert Meetings/Workshops will focus on specific targets and bring together structural biologists/biochemists with chemists from academia and the pharmaceutical industry.Drug Evaluation (Working Group 3)
The rationally or empirically identified inhibitors will need to show activity against the relevant stage of the parasite in in vitro and subsequently in in vivo models of infection. New models and assays need to be developed to measure selectivity of activity and increase throughput. Methods need to be developed to determine drug levels at sites of infection and to target drugs to infected tissues. This approach is important for both new lead compounds and of compounds with activity for other indications that deserve further development. Expert Meetings/Workshops will focus upon the improvement of assays and the design of compounds with appropriate distribution to the sites of infection within the host.Preclinical Development (Working Group 4)
Most preclinical development (pharmacology, toxicology, scale-up chemistry) can only be performed by the pharmaceutical industry and/or specialised contract houses because of expertise, facilities and costs. Outside industry groups can establish optimal existing drug regimes, drug formulations, drug combinations, analytical techniques, pharmacokinetic factors that relate efficacy to tissue levels and drug metabolism. The Expert meetings will bring together teams working on lead compounds with pharmaceutical company and public &endash; private partnership representatives to focus on the optimisation of leads to ensure that they are candidate drugs with the properties attractive to the pharmaceutical industry.Drug Resistance (Working Group 5)
Acquired drug resistance has become a major problem in all areas of antimicrobial drug treatment and is one of the main driving forces for drug discovery research. Although drug resistance is a major problem in antiparasitic treatment, in particular antimalarials, few mechanisms involved in resistance development have been described. Drug resistance is a problem that spans the expertise present in all the areas identified above (I to IV) in relation to mutational changes in drug targets, drug design to overcome resistance and drug combinations. Resistance modifiers that restore the effectiveness of present first line drugs would be of great practical interest, but no compounds have yet proven effective at therapeutic doses. Expert Meetings are an ideal way of bringing together cross-disciplinary teams to focus on particular problems of drug resistance.
The Annual Congress will provide the focus for European scientists working on anti-parasitic drug development to present their work, meet other scientists and develop networks. Plenary lectures will present and review the most recent significant developments in target validation and drug development. The previous COST Action B9 established a series of annual meetings that attracted leading scientists from North America, Asia, South America and Africa. The Annual Congress is an opportunity to maintain this trend so that research contacts can be extended to other laboratories with expertise and to endemic countries.
The Annual Congress also provides the mechanism for forging links with other international organisations. In particular the Congress will invite representatives from:
· WHO Tropical Diseases Research Programme (TDR), Geneva
· Medicines for Malaria Venture (MMV), Geneva
· International Organisation for Chemistry in Development (IOCD)
· Medicines sans Frontieres/Drugs for Neglected Diseases Group, Brussels
· IFPMA/EFPMA
· EC DG12
The representatives from these bodies will be invited as Official Observers and a specific briefing meeting will be held with the MC at each Congress to encourage links and enable mutual priorities (without overlap) to be established.
Notification of the Congress will be sent to all Co-ordinators of projects under the EU's 5th and 6th Framework Programmes.
Exchange of knowledge and technical skills and access to specialist facilities are essential to scientific progress. Short term scientific missions for junior scientists and technicians will be supported for:
· training in specific skills
· development of joint research projects
· development of contacts for furtherance of research careers in Europe
4: Support for Scientific Research
The COST Action does not itself provide financial support for research activities. However, the group of scientists who interact and develop collaborations through the Action, either as MC or through regular participation in COST activities, represents a considerable body of expertise ranging from molecular biology to chemistry to pharmacology. The integration of a group of European scientists that have proven research productivity will add to applications for financial support for research projects. A compendium of expertise and links between groups will be produced in electronic and paper formats. This will be available through the organiser of the new COST Action and will be circulated to both small and large pharmaceutical companies (for example GSK, Aventis, 4SC) in the EC.