Drug discovery and development for schistosomiasis: From repositioning of antimalarial drug leads and clinical advanced drug candidates to the development of a new paediatric formulation of praziquantel
The aim of my 4-year research project is to identify one or several antischistosomal drug development candidates targeting the haemoglobin degradation pathway and/or other mechanisms with favourable physico-chemical and drug metabolism and pharmacokinetics (DMPK) properties. My proposed research will assist in improving current treatment options for schistosomiasis (and other trematodiases, such as opisthorchiasis). To accomplish this aim, I will pursue four specific objectives:
i. To assess the in vitro activity of analogues of selected lead compounds against larval (schistosomula) and adult S. mansoni and assess cytotoxicity and metabolic stability.
ii. To elucidate and characterize in vivo efficacy of lead compounds in schistosome-rodent models.
iii. To determine pharmacokinetic parameters for the most potent compounds.
iv. To determine the activity, safety and pharmacokinetics of escalating dosages of a new ODT of praziquantel in preschool-aged children infected with S. haematobium in Côte d’Ivoire and S. mekongi (and Opisthorchis viverrini) in Laos.