Data di Pubblicazione:
2013
Citazione:
CRIMALDDI: platform technologies and novel anti-malarial drug targets / H. Vial, D. Taramelli, I.C. Boulton, S.A. Ward, C. Doerig, K. Chibale. - In: MALARIA JOURNAL. - ISSN 1475-2875. - 12:1(2013 Nov), pp. 396.1-396.11.
Abstract:
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
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
CRIMALDDI ; Malaria ; Drug discovery ; Research agenda ; Novel targets ; Enabling technologies ; Prioritization
Elenco autori:
H. Vial, D. Taramelli, I.C. Boulton, S.A. Ward, C. Doerig, K. Chibale
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