Fexinidazole – A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness

This article describes the preclinical profile of fexinidazole, a new drug candidate with the potential to become a novel, oral, safe and effective short-course treatment for curing both stage 1 and 2 human African trypanosomiasis and replace the old and highly problematic treatment modalities available today. Fexinidazole is orally available and rapidly metabolized in two metabolites having equivalent biological activity to the parent and contributing significantly to the in vivo efficacy in animal models of both stage 1 and 2 HAT. Animal toxicology studies indicate that fexinidazole has an excellent safety profile, with no particular issues identified. Fexinidazole is a 5-nitroimidazole and, whilst it is Ames-positive, it is devoid of any genetic toxicity in mammalian cells and therefore does not pose a genotoxic risk for use in man. Fexinidazole, which was rediscovered through a process of compound mining, is the first new drug candidate for stage 2 HAT having entered clinical trials in thirty years, and has the potential to revolutionize therapy of this fatal disease at a cost that is acceptable in the endemic regions

Boldness-exploration behavioral syndrome: interfamily variability and repeatability of personality traits in the young of the convict cichlid (Amatitlania siquia).

9 pagesInternational audienceIn recent years, considerable research interest in behavioral ecology has focused on characterizing and understanding individual differences in behavior that are consistent over time and across contexts, termed animal “personalities,” and correlations between various behaviors across contexts, termed behavioral syndromes. Although there is some evidence that differences in personality among individuals within populations can be genetically based and adaptive, when and how individual personality differences emerge in a population is not well understood, but of considerable general interest. Here, using juveniles of the convict cichlid (Amatitlania siquia) as a model system, we investigated in the laboratory whether individuals consistently differ in their personalities and whether behavioral syndromes are apparent at an early developmental stage and, if so, whether distinct personality traits are heritable. Under standardized laboratory conditions and using sibling analysis, we quantified interindividual differences in their boldness behavior under potential predation threat and their exploratory activity in a novel environment, 2 ecologically important behaviors, as our focal personality traits and estimated their respective repeatability and heritability. We report for the first time consistent (repeatable) and heritable individual differences in boldness and exploratory behaviors, and a boldness–exploration behavioral syndrome, in young convict cichlids. Bolder fish were more exploratory than relatively timid ones. These results provide novel evidence for the emergence in early life history of consistent individual differences in personality traits and behavioral syndromes in this species and suggest that genetic variation for boldness and exploratory behaviors, and thus potential for selection on these traits, exists in our study population