This creates a critical need to identify new drug targets and agents that can effectively treat the disease.
Building on Recent Discoveries
The current study builds on recent research that has implicated chitin metabolism in the larval development of the parasite O. volvulus.
Chitin is the protective outer covering that forms part of O. volvulus's outer cuticle. While knowledge of chitin biosynthesis in nematodes is limited, scientists do know that two classes of enzymes are critical for maintenance of the pathwaychitin synthases and chitinases, digestive enzymes that break down glycosidic bonds in chitin. The dynamic synthesis and degradation of chitin by these enzymes is a prerequisite for the organism's development and therefore a potential drug target.
Researchers in the field had recently identified and characterized one interesting chitinase from O. volvulus, OvCHT1. Although OvCHT1's exact metabolic role is not known, it was found to be expressed only in the infective L3 larvae and to have potential involvement in host transmission, molting, and important developmental processes in the parasite. Immunoelectron microscopy analysis detected chitinase in the pharyngeal glands of O. volvulus, structures that may contain a wide variety of proteins essential for the remodeling processes during molting and the shedding of the old cuticle.
"Therefore, we focused on these enzymes," Gloeckner says, "and reasoned that inhibiting them may eliminate onchocerciasis."
To test these enzyme candidates, Gloeckner, Janda and their colleagues used the Johns Hopkins clinical compound librarywhich contains 1,514 compounds, of which 1,082 are U.S. Food and Drug Administration (FDA)-approve
|Contact: Keith McKeown|
Scripps Research Institute