filariasiswho tdr stammers Wuchereria bancrofti: microfilarial worm in blood. Credit: WHO/TDR/Stammers 
worminator 300x400The first generation Worminator built in CDIPD and configured to detect large Brugia adult parasites.

The CDIPD coordinates a large collaborative project involving scientists from the Lindsley F. Kimball Research Institute New York Blood Center; University of Buea, Cameroon; Anacor Pharmaceuticals, Inc., Palo Alto, CA; University of California Santa Cruz; The Structural Genomic Consortium; and University of California San Francisco. The aim of the project, funded by the Bill & Melinda Gates Foundation, is to develop drugs for the treatment of two devastating diseases: river blindness and lymphatic filariasis, caused by filarid nematodes: River Blindness (caused by Onchocerca volvulus) and Lymphatic Filariasis (caused by Brugia malayi and Wuchereria bancrofti). Drugs in current use kill the microfilariae (larval) stages of the parasite, but treatment is desperately needed to kill the adult worm for cure and stop transmission.

A video imaging system, the "Worminator", was designed by Chris Marcellino to assay compound libraries versus large parasites such as adult Brugia which are about 2-3 inches long. The Worminator detects and quantifies the parasites movements simultaniously in the entire culture plate.

The CDIPD in collaboration with the UCSD Bioengineering Department is now building next edition of Worminator featuring a newer video camera and computer. Originally configured to allow analysis of large Brugia adult parasites, it is being modified to allow analysis of the smaller schistosome and C. elegans organisms.

pipeline 720x38
  • Novel target identified from Anacor screening
  • Anacor compound collection
  • FDA-approved compounds
  •  Auranofin
 

PUBLICATIONS

Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis. PLoS Negl Trop Dis. 2015 Feb;9(2):e0003534. doi: 10.1371/journal.pntd.0003534. Bulman CA, Bidlow CM, Lustigman S, Cho-Ngwa F, Williams D, Rascón AA Jr, Tricoche N, Samje M, Bell A, Suzuki B, Lim KC, Supakorndej N, Supakorndej P, Wolfe AR, Knudsen GM, Chen S, Wilson C, Ang KH, Arkin M, Gut J, Franklin C, Marcellino C, McKerrow JH, Debnath A, Sakanari JA.

A gene family of cathepsin L-like proteases of filarial nematodes are associated with larval molting and cuticle and eggshell remodeling. Mol Biochem Parasitol. 2004 Aug;136(2):227-42. Guiliano DB, Hong X, McKerrow JH, Blaxter ML, Oksov Y, Liu J, Ghedin E, Lustigman S.

Do filarid nematodes have a vascular system? Parasitol Today. 1999 Mar;15(3):123. No abstract available. McKerrow JH, Huima T, Lustigman S.

Brugia pahangi: identification and characterization of an aminopeptidase associated with larval molting. Exp Parasitol. 1993 Mar;76(2):127-33. Hong X, Bouvier J, Wong MM, Yamagata GY, McKerrow JH.