We are currently working on a project to discover new and improved drugs for treating schistosomiasis.
The project is in collaboration with Dr Quentin Bickle at the London School of Hygiene and Tropical Medicine, UK (see website) and is funded for 3½ years by the Medical Research Council, UK.
Schistosomiasis (also known as bilharzia) is a severe parasitic disease affecting over 200 million people mainly in poor countries of sub-saharan Africa resulting in 300,000 deaths per year1. In addition to mortality, schistosomiasis is a chronic condition that has been classified as the second most socioeconomically devastating disease after malaria2. The disease is carried by freshwater snails and humans become infected after exposure to contaminated water. The parasite causes damage to internal organs.
Treatment currently relies on a single drug, praziquantel (PZQ). Although it is usually successful, it only kills adult worms leaving any juvenile worms to continue to develop in the body. In addition, praziquantel tablets are large and bitter tasting which make them sub-optimal for pediatric use and there are also concerns about development of resistance arising from mass administration of a single agent. We are therefore seeking new drugs which address these limitations of praziquantel.
Dr Bickle has developed a high content assay using Schistosoma mansoni larvae, which for the first time enables high throughput screening against larval forms of the parasite3. His laboratory also runs assays for adult worms and an in vivo mouse infection model. Several compound libraries have been screened, initially in the larval assay at LSHTM. We have published the structures of several hits4, which have also been included in MMV's pathogen box5. Subsequent Medicinal chemistry on the hits has been led by Salvensis.
1 World Health Organisation "Schistosomiasis".
2 The Carter Center "Schistosomiasis Control Program".
3 PLOS Neglected Diseases "Whole Organism High-Content Screening by Label-Free, Image-Based Bayesian Classification for Parasitic Diseases".
4 PLOS Neglected Diseases "High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni".
5 Pathogen Box "Pathogen Box"