Bill and Melinda Gates Foundation:
Development of a Macrofilaricidal Drug Candidate for the Treatment of Human Onchocerciasis
- Bill and Melinda Gates Foundation
- Award Number: OPP1017584
- Principal Investigator: J. McKerrow (UCSF)
- Co-PIs: E. Easom (Anacor), S. Lustigman (Lindsey F. Kimball Research Institute, N.Y. Blood Center) and R. Singh (SFSU)
Onchocerciasis is the world's second leading infectious cause of blindness and is an eye and skin disease caused by a nematode worm known scientifically as Onchocerca volvulus. The World Health Organization's (WHO) expert committee on onchocerciasis estimates the global prevalence is 17.7 million of whom about 270,000 are blind and another 500,000 have visual impairment. About 99% of infected persons are in Africa; the remainder are in Yemen and six countries in the Americas. This research effort brings together a team of leading medicinal chemists, biologists, and computer scientists to research and deliver a macrofilaricidal drug candidate for the treatment of onchocerciasis in humans that is ready for preclinical toxicology studies in 24 months. While the primary focus is development of a macrofilaricidal drug candidate for the treatment of onchocerciasis, it is expected that parallel screening of the closely related filarid, Brugia malayi will also yield drug candidates for the treatment of lymphatic filariasis, a disfiguring and disabling neglected parasitic disease. The key objectives of this project include: (1) screening, (2) hit-to-lead (HTL) Chemistry, (3) lead optimization, (4) mechanism of action studies, and (5) nematode helminth phenotype-based high-throughput Screening technology/ assay development.
Computational drug discovery against Filariasis and Onchocerciasis.
- H. Lee*, A. Moody-Davis, U. Saha, B. Suzuki, D. Asarnow, S. Chen, M. Arkin, C. Caffrey, and R. Singh*, "Quantification and Clustering of Phenotypic Screening Data Using Time Series Analysis for Chemotherapy of Schistosomiasis", BMC Genomics, 12 (Suppl 1):S4, 2012 (*H. Lee and R. Singh equal contributors. Corresponding author R. Singh).
- C. Marcellino, J. Gut, K. C. Lim, R. Singh, J. McKerrow, J. Sakanari, "WormAssay: A Novel Computer Application for Whole-Plate Screening of Macroscopic Parasites", PLoS Neglected Tropical Diseases, Accepted. To appear in 2012.
- R. Singh, "Quantitative High-Content Screening-Based Drug Discovery against Helmintic Diseases", in Target Validation, Drug and Vaccine Development for Helminth Diseases, C. Caffrey and P. Selzer eds., Wiley 2012 (To Appear).