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Schistosomiasis affects hundreds of millions of people worldwide, mostly in the world’s poorest countries. Praziquantel (PZQ) is the only medication currently used in mass drug administration programs, raising the risk of drug resistance. There is a critical need to develop new therapeutics that target essential pathways that are not affected by PZQ. Prof. Fabrice Boyom at the University of Yaoundé I is interested in leveraging the therapeutic properties of local plants and other natural products to treat parasitic diseases. With support from Merck KGaA, Darmstadt, Germany, Dr. Jennifer Keiser at the Swiss Tropical and Public Health Institute will screen selected natural product extracts collected by Prof. Boyom for antischistosomal activity.

Dr. Keiser is the Head of the Helminth Drug Development Unit at Swiss TPH. Dr. Keiser’s research is focused on drug discovery for helminth infections, and she evaluates compounds using both in vitro and in vivo assays. BVGH connected Dr. Keiser with Dr. Quinn, Director of the Eskitis Institute, who facilitated the sharing of a targeted selection of Nature Bank isolates for Dr. Keiser to screen against Schistosoma and Ancylostoma (hookworm).

Key Personnel: Michael Pollastri (Northeastern University), Jean-Robert Ioset (DNDi), Byron Arana (DNDi), Marcel Kaiser (Swiss TPH). Dr. Pollastri had identified promising compounds in a screen against Leishmania major (the pathogen that causes cutaneous leishmaniasis). To support drug development efforts against additional neglected diseases, Dr. Pollastri shared his screening data with Drs. Arana and Ioset. With this data, Drs. Arana and Ioset connected with Dr. Kaiser, who screened the compounds for activity against Trypanosoma cruzi, T. brucei, L. donovani, and Plasmodium falciparum. Dr. Kaiser further conducted counter screens to assess cellular cytotoxicity.

Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical disease that, if left untreated, can cause debilitating skin ulcers and destruction of soft tissue. Current treatment involves eight weeks of antibiotics, a difficult course to implement in resource-limited settings. Drs. Pluschke and Scherr were interested in screening compounds against Buruli ulcer that had showed promise in screens against M. tuberculosis, as M. ulcerans is closely related to M. tuberculosis. BVGH facilitated a collaboration with AstraZeneca, which shared 100 anti-tuberculosis compounds (including one in clinical trials) for the Swiss TPH investigators to screen in their Buruli ulcer assay. While a number of potent antitubercular agents were only weakly active or inactive against M. ulcerans, five compounds showed high activity, making screening of focused antitubercular libraries a good starting point for lead generation against M. ulcerans.

Soil-transmitted helminthiases, caused by multiple species of parasitic worms, affect more than 1.5 billion people, or nearly 25% of the world’s population. Dr. Keiser, Head of the Helminth Drug Development Unit at Swiss TPH, maintains in vitro and in vivo assays for a wide range of helminth life cycles. As part of its commitment to advancing global public health and accelerating discovery of new treatments for neglected diseases, J&J shared JNJ-46336173, a nicotinic acetylcholine receptor (nAChR) agonist, and over 100 analogs thereof, with Dr. Keiser through WIPO Re:Search. Dr. Keiser screened these compounds for activity against three parasitic helminth species.

Dr. Keiser, Head of the Helminth Drug Development Unit at Swiss TPH, maintains in vitro and in vivo assays for a wide range of helminth life cycles. BVGH reviewed a publication detailing the effect of nicotinic acetylcholine receptor (nAChR) agonists on rat hookworm, and contacted Dr. Keiser to gauge her interested in screening related compounds. Dr. Keiser expressed interest, and Pfizer provided seven nAChR agonists that Dr. Keiser screened in her assays against Necator americanus, Ancylostoma ceylanicum, and Heligmosomoides polygyrus.

Drs. Pluschke and Scherr at the Swiss TPH were interested in repurposing tuberculosis drugs to treat Buruli ulcer, a bacterial infection caused by Mycobacterium ulcerans. BVGH connected Drs. Pluschke and Scherr with Drs. Thompson and Ramon-Garcia at UBC, who had discovered that certain avermectins showed promising activity against M. tuberculosis and other mycobacterial species. The UBC investigators shared eight avermectins with Drs. Pluschke and Scherr, who tested the compounds for their activity in an in vitro screen against clinical isolates of M. ulcerans.