Drug development for onchocerciasis-the past, the present and the future

Abstract

Onchocerciasis affects predominantly rural communities in Africa, and with small foci in South America and the Yemen. The disease is a major cause of blindness and other significant morbidity and mortality. Control programs have achieved a major impact on the incidence and prevalence of onchocerciasis by interrupting transmission with vector control programs, and treatment with mass drug administration using the microfilaricide ivermectin. Over the last few decades, several microfilaricides have been developed. This initially included diethylcarbamazine, which had significant side effects and is no longer used as such. Ivermectin which is a safe and highly effective microfilaricide and moxidectin which is a longer acting microfilaricide are presently recognized therapies. Suramin was the first effective macrofilaricide but was prohibitively toxic. Certain antibiotics including doxycycline can help eliminate adult worms by targeting its endosymbiont bacteria, Wolbachia pipientis. However, the dosing regimens may make this difficult to use as part of a mass disease control program in endemic areas. It is now widely recognized that treatments that are able to kill or permanently sterilize adult filarial worms should help achieve the elimination of this disease. We summarize in detail the historic drug development in onchocerciasis, including prospective future candidate drugs.

Repurposing of Anti-infectives for the Management of Onchocerciasis using Machine Learning and Protein Docking Studies

“…Figure S3 in SI is LD2 vs LD3 plot of the LDA model showing the location of oncho + (red) , oncho - (blue) and test drugs (orange) . It must be highlighted here that doramectin and pyrvinium with known oncho + were added to investigate whether this approach would have identified them as potentially useful drugs 65,66 .…”

Onchocerciasis Drug Discovery: In Vitro Evaluation of FDA-Approved Drugs against Onchocerca gutturosa in Gambia

“…With the urgent need to identify drugs with potential macrofilaricidal activity against Onchocerca parasites, using the strategy of drug repurposing to identify new drugs for the prompt development of therapeutics for the treatment of filariasis is not a new concept; indeed, the drugs currently in use to treat filarial infections, ivermectin, diethylcarbamazine, moxidectin and doxycycline, have all been repurposed from the veterinary or medical fields [ 14 ]. Previous studies have screened libraries and drugs for activity against filarial parasites [ 15 ] and the Pharmakon 1600 library itself has also been screened for antischistosomal activity [ 16 ].…”

Onchocerciasis Drug Discovery: In vitro Evaluation of FDA- Approved Drugs against Onchocerca gutturosa in Gambia

“…With the urgent need to identify drugs with potential macrofilaricidal activity against Onchocerca parasites, using the strategy of drug repurposing to identify new drugs for prompt development of therapeutics for the treatment of filariasis is not a new concept; indeed, the drugs currently in use to treat filarial infections, ivermectin, diethylcarbamazine, moxidectin and doxycycline have all been repurposed from the veterinary or medical fields [15]. Previous studies have screened libraries and drugs for activity against filarial parasites [16] and the Pharmakon 1600 library itself has also been screened for antischistosomal activity [17].…”