Our Onchocerciasis Research

River BlindnessSome chidren with River Blindness are restrained to prevent them from injuring themselves or wandering off. Credit: Science

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 California Institute for Biomedical Research (CALIBR); San Francisco State University; and UC 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: Onchocerca volvulus (River Blindness) and Brugia malayi and Wuchereria bancrofti (Lymphatic Filariasis). Drugs in current use kill microfilariae (larval) stages of the parasites, but treatment is desperately needed to kill the adult worm for cure and to stop transmission.

Dr. Sara Lustigman of the NY Blood Center (Lindsley F. Kimball Research Institute) is screening compounds against the L3 stage of O. volvulus. Dr. Fidelis Ngwa at University of Buea, Cameroon, is screening hits identified against Brugia worms against Onchocerca adults and Loa loa microfilariae.

 

pipeline 720x38
  • Novel target identified from Anacor library screening
  • Anacor compound collection
  • FDA-approved library
  • PDE4 inhibitors
  • 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.

Simulium damnosum s.l.: isolation and identification of prophenoloxidase following an infection with Onchocerca spp. using targeted differential display. Exp Parasitol. 1997 Jul;86(3):213-8. Hagen HE, Kläger SL, McKerrow JH, Ham PJ.

Cloning of a cysteine protease required for the molting of Onchocerca volvulus third stage larvae. J Biol Chem. 1996 Nov 22;271(47):30181-9. Erratum in: J Biol Chem 1997 Feb 14;272(7):4645. Lustigman S, McKerrow JH, Shah K, Lui J, Huima T, Hough M, Brotman B.

Simulium damnosum s.l.: identification of inducible serine proteases following an Onchocerca infection by differential display reverse transcription PCR. Exp Parasitol. 1995 Nov;81(3):249-54. Hagen HE, Kläger SL, Chan V, Sakanari JA, McKerrow JH, Ham PJ.

Molecular cloning and characterization of onchocystatin, a cysteine proteinase inhibitor of Onchocerca volvulus. J Biol Chem. 1992 Aug 25;267(24):17339-46. Lustigman S, Brotman B, Huima T, Prince AM, McKerrow JH.

Extracellular proteases of Onchocerca. Exp Parasitol. 1989 Feb;68(2):176-85. Lackey A, James ER, Sakanari JA, Resnick SD, Brown M, Bianco AE, McKerrow JH.