Developing a Macrofilaricidal Drug for Onchocerciasis Using Anacor's Novel Oxaborole Technology

Sponsor: Bill & Melinda Gates Foundation

Location(s): United States


Onchocerciasis, also known as river blindness and Robles disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode (roundworm). Onchocerciasis is second in the world only to trachoma as an infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that causes the severe inflammatory response that leaves many blind. The parasite is transmitted to humans through the bite of a black fly of the genus Simulium. The larval nematodes spread throughout the body. When the worms die, their Wolbachia symbionts are released, triggering a host immune system response that can cause severe itching, and can destroy optical tissue in the eye.

Most infections occur in sub-Saharan Africa, although cases have also been reported in Yemen and isolated areas of Central and South America. As of 2001, an estimated 18 million people suffered from onchocerciasis, with approximately 270,000 cases of blindness related to the infection.

Dr Mckerrow has been involved in the development of oxaborole drugs, which were originally screened for activity against T. brucei at UCSF.  In pre-clinical studies, they were shown to be safe and efficacious to treat T. brucei as it is able to cross the blood-brain barrier. In 2011, regulatory toxicology studies were performed to assess the compound’s safety, and the drug has moved to First-in-Human studies.

As the Oxaborole drugs move to approval, they are being screened for activity against Onchocerca volvulus.