GENERAL

Established that cysteine proteases are key to the survival of many disease pathogens and that they represent excellent targets for developing new drugs. Proof-of-concept generated, for example, in animal models for African trypanosomiasis, cryptosporidiosis, Chagas disease, schistosomiasis and hookworm infection.

 

AMEBIASIS

A shotgun DNA microarray for Entamoeba histolytica was developed for the first time and this new tool provided important clues about how a pathogen orchestrates responses to the host environment. 

Repurposing of the arthritis drug, auranofin, to treat several parasitic infections. Auranofin was identified in the first high-throughput screen of Entamoeba histolytica, the causative agent of enteric amebiasis. Based on CDIPD advocacy, the drug received Orphan Drug Status from the Food & Drug Administration (FDA) for treatment of amebiasis. Auranofin has also completed clinical trials for treatment of giardiasis in Bangladesh. 

CHAGAS DISEASE

With collaborators at Anacor Pharmaceuticals (now Pfizer), discovered an oxaborole small molecule that kills Trypanosoma brucei, the causative agent of human African trypanosomiasis (Sleeping sickness). The discovery subsequently led to the clinical development of acoziborole as the first single-dose oral therapy for this deadly disease.

The remarkable story of the cysteine protease inhibitor, K11777, which was originally programmed for treatment of Chagas disease at the Center, and its subsequent reincarnation as a clinical candidate for treatment of coronavirus (covid-19) disease.  

NAEGLERIASIS

Discovery of natural product, corifungin, as a drug lead for Naegleria infection which causes primary amebic meningoencephalitis (PAM), a deadly disease that occurs most often in children and young adults swimming in contaminated freshwater bodies. Corifungin was also shown to have strong activity against Leishmania donovani which causes visceral leishmaniasis. Based on CDIPD advocacy, corifungin received Orphan Drug Status from the FDA for treatment of PAM and visceral leishmaniasis.

SCHISTOSOMIASIS

Discovery with colleagues at McGill University that the adult schistosome flatworm parasite has a sophisticated double-brain that allows for independent coordination of its oral and ventral suckers. Proper sucker control is vital to the worm’s ability to migrate around the venous blood system, including in relation to laying its eggs.

Discovered that the adult male schistosome can sense its environment and change how it moves through blood vessels. It can coordinate its ventral and oral suckers to “march,” or, in tighter spaces such as in small venules, can use body wave peristalsis to squeeze into small venules. The parasite can also reverse that peristalsis to exit tight spaces.