Preclinical progression of novel anti-trypanosomal nucleoside 'lead' series towards veterinary application.

Within ongoing collaborative research with the Lab. of Medicinal Chemistry (UGent), a series of novel nucleoside analogues was identified to have potent and selective in vitro activity against African Trypanosomes, which was also confirmed in vivo in an acute and a chronic mouse model of Trypanosoma brucei. A basic dataset supporting early preclinical exploration is already available: oral availability, metabolic stability, blood-brain barrier passage, cidal and curative potential and mechanism of action. Project valorization potential must currently be situated in the veterinary application area in view of its economical and societal impact, and much less in the human application. In order to formally upgrade this project to 'drug development candidate' status, additional preclinical exploration is required to reach a go / no-go decision and trigger a commitment of a committed public-private partnership (GALVmed). In line with their preferred target product profile (TPP), the proposed research will involve in vitro and in vivo pharmacology extended to the animal trypanosome species, absorption and elimination pharmacokinetics after oral and parenteral (single dose) administration, in vitro metabolic half-life in the target animal species (cattle, horse), genotoxicity (Ames test) and short term (2w) repeated-dose toxicity in mice.

Keywords:PRECLINICAL RESEARCH, ANIMAL TRYPANOSOMES

Disciplines:Tropical medicine, Parasitology