CRIMALDDI: a co-ordinated, rational, and integrated effort to set logical priorities in anti-malarial drug discovery initiatives (original) (raw)
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While malaria research has traditionally been strong in Europe, targeted and sustained support for cooperative malaria research at EU level, namely through the EU's 6th and 7th Framework Programmes for research and technological development, FP6 (2002) and FP7 (2007-2013, has boosted both impact and visibility of European malaria research. Most of the European malaria research community is now organized under a number of comprehensive and complementary research networks and projects, assembled around four key areas:
The American journal of tropical medicine and hygiene, 2007
Malaria is a major public health problem; about half of the world's populations live under exposure. The problem is increasing in magnitude and complexity because it is entwined with low socio-economic status, which makes African women and children particularly vulnerable. Combating malaria therefore requires concerted international efforts with an emphasis on Africa. The Multilateral Initiative on Malaria (MIM) was founded in 1997 to meet that need through strengthening research capacity in Africa, increasing international cooperation and communication, and utilization of research findings to inform malaria prevention, treatment, and control. The review undertaken in 2002 showed that through improved communication and science-focused institutional networks, MIM had brought African scientists together, opened up communication among malaria stakeholders, and provided Internet access to literature. The achievements were made through four autonomous constituents including the coord...
Repositioning: the fast track to new anti-malarial medicines?
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Drug discovery for malaria: a very challenging and timely endeavor
The prevalence of resistance to known antimalarial drugs has resulted in the expansion of antimalarial drug discovery efforts. Academic and nonprofit institutions are partnering with the pharmaceutical industry to develop new antimalarial drugs. Several new antimalarial agents are undergoing clinical trials, mainly those resurrected from previous antimalarial drug discovery programs. Novel antimalarials are being advanced through the drug development process, of course, with the anticipated high failure rate typical of drug discovery. Many of these are summarized in this review. Mechanisms for funding antimalarial drug discovery and genomic information to aid drug target selection have never been better. It remains to be seen whether ongoing efforts will be sufficient for reducing malaria burden in the developing world.
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Historically, one of the key problems in neglected disease drug discovery has been identifying new and interesting chemotypes. Phenotypic screening of the malaria parasite, Plasmodium falciparum has yielded almost 30,000 submicromolar hits in recent years. To make this collection more accessible, a collection of 400 chemotypes has been assembled, termed the Malaria Box. Half of these compounds were selected based on their drug-like properties and the others as molecular probes. These can now be requested as a pharmacological test set by malaria biologists, but importantly by groups working on related parasites, as part of a program to make both data and compounds readily available. In this paper, the analysis and selection methodology and characteristics of the compounds are described.
CRIMALDDI: platform technologies and novel anti-malarial drug targets
Malaria Journal, 2013
The Coordination, Rationalization, and Integration of antiMALarial drug Discovery & Development Initiatives (CRIMALDDI) Consortium, funded by the EU Framework Seven Programme, has attempted, through a series of interactive and facilitated workshops, to develop priorities for research to expedite the discovery of new antimalarials. This paper outlines the recommendations for the development of enabling technologies and the identification of novel targets. Screening systems must be robust, validated, reproducible, and represent human malaria. They also need to be cost-effective. While such systems exist to screen for activity against blood stage Plasmodium falciparum, they are lacking for other Plasmodium spp. and other stages of the parasite's life cycle. Priority needs to be given to developing high-throughput screens that can identify activity against the liver and sexual stages. This in turn requires other enabling technologies to be developed to allow the study of these stages and to allow for the culture of liver cells and the parasite at all stages of its life cycle. As these enabling technologies become available, they will allow novel drug targets to be studied. Currently antimalarials are mostly targeting the asexual blood stage of the parasite's life cycle. There are many other attractive targets that need to be investigated. The liver stages and the sexual stages will become more important as malaria control moves towards malaria elimination. Sexual development is a process offering multiple targets, even though the mechanisms of differentiation are still not fully understood. However, designing a drug whose effect is not curative but would be used in asymptomatic patients is difficult given current safety thresholds. Compounds active against the liver schizont would have a prophylactic effect and Plasmodium vivax elimination requires effectors against the dormant liver hypnozoites. It may be that drugs to be used in elimination campaigns will also need to have utility in the control phase. Compounds with activity against blood stages need to be screened for activity against other stages. Natural products should also be a valuable source of new compounds. They often occupy non-Lipinski chemical space and so may reveal valuable new chemotypes.
The American journal of …, 2007
The Multilateral Initiative on Malaria was created after an international conference on malaria in Africa held in Dakar, Senegal, in early 1997. The main goal of the conference was to "strengthen and sustain, through collaborative research and training, the capability of malaria endemic countries in Africa to carry out research required to develop or improve tools for malaria control." This conference marked the beginning of a new global focus on malaria research and capacity building three decades after a partially successful global malaria eradication program. In addition to promoting research on and institutional strengthening for malaria, the initiative was created to develop mechanisms and systems to facilitate timely communication of information to scientists working in Africa, enhance the capacity to conduct malaria collaborative/multi center research in Africa, and promote application of research results to address malaria control needs. This report summarizes the increased malaria research capacity and empowerment of African researchers facilitated by the Multilateral Initiative on Malaria through the Special Program for Research and Training in Tropical Disease Research at the World Health Organization.