Now scientists at the Scripps Research Institute, lead by Dr. Christian Gloeckner have discovered a potential new use for the drug closantel, i.e., the drug may be useful in combating river blindness, a tropical disease that is the world's second leading infectious cause of blindness for humans.
River blindness is caused by thread-like filarial nematode worms, Onchocerca volvulus, which are transmitted among humans through the bite of a black fly. The nematodes then multiply and spread throughout the body. When they die, they cause a strong immune system response that can destroy surrounding tissue, including that of the eye. Currently, the only drug available for mass treatment of river blindness is ivermectin and it now appears that resistance to that drug is emerging.
River blindness is caused by thread-like filarial nematode worms, Onchocerca volvulus, which are transmitted among humans through the bite of a black fly. The nematodes then multiply and spread throughout the body. When they die, they cause a strong immune system response that can destroy surrounding tissue, including that of the eye. Currently, the only drug available for mass treatment of river blindness is ivermectin and it now appears that resistance to that drug is emerging.
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 pathway chitin 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. Therefore, researchers focused on these enzymes.
In this method, chitinase's enzymatic activity was monitored by a fluorescent signal (when a huge decrease in the signal was observed the enzyme was essentially knocked-out). Researchers tried in vivo method (Closantel, completely prevented molting from the L3 to L4 stage) also. As per the claim by the researchers, out of levfloxacin, lomefloxacin, dexketoprofen, and closantel (tried), only closantel was found to exhibit potent enough inhibition to warrant further investigation.
Researchers conclude that based on its specificity, potency, and ease of synthesis, closantel or one its analogues might represent a promising alternative or adjunct therapy in combination with ivermectin for the treatment of onchocerciasis....
Ref : Christian Gloeckner et. al., Proceedings of the National Academy of Sciences (PNAS)
