Identification and characterization of new drug targets in the nematode Onchocerca volvulus to combat "river blindness" (onchocerciasis)

• Applicant: Dr. Christian Glöckner
• Subject Area: Biochemistry ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2008 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 81938116

The parasitic nematode Onchocerca volvulus is the causative agent of onchocerciasis or “river blindness”. It is a chronic and slowly progressing disease that is characterized by eye affections and skin lesions with severe troublesome itching. Onchocerciasis occurs in 30 countries of the tropical sub–Saharan Africa where 18 million people are currently infested. Of these, 4 million patients have skin manifestations and 2 million are blind or severely visually impaired.1 Detailed knowledge of indispensible metabolic pathways for the nematode’s development and / or survival will provide new insights for the identification of new drug targets. Since the nematode development is largely dependent on chitin metabolism, inhibition, or deregulation of enzymes in this pathway are important objectives for the development of therapeutic agents, not least because chitin polymers are absent in vertebrates. Three key enzymes will be targeted to identify and characterize inhibitors of the chitin metabolism from small molecule chemical compound libraries using high through-put (HTP) in vitro assays. A second approach is to target the bacterial endosymbiont Wolbachia of O. volvulus, as recently reported data demonstrate that eradication of the endosymbiont leads to significant reduction of filarial viability.2,3 Using HTP in vitro assays, specifically designed collections of small organic molecules will be searched for Wolbachia-specific antibiotic agents with the potential to circumvent the undesired effects of non-specific killing of the patient’s microflora by targeting type II FAS enzymes. Type II FAS (fatty acid synthase) consists of several discrete enzymes and is characteristic to bacteria.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Kim Janda, Ph.D.