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.
Alnylam will design and synthesize optimized siRNAs for an NII researcher to assess regulation of host hepatocyte genes during liver-stage malaria. A Northeastern University researcher will encapsulate the siRNAs for targeted delivery to hepatocytes.
Drs. Meyers and Wildman were interested in the potential of PDE inhibitors to target a specific protein of interest in Mycobacterium tuberculosis (MTb). BVGH connected them with Dr. Pollastri, who had synthesized a set of PDE inhibitors as potential new drugs for HAT. Dr. Pollastri shared the structures of his compounds with Drs. Meyers and Wildman, who performed virtual docking studies to predict whether the inhibitors might have activity against MTb.
Dr. Pollastri is a medicinal chemist specializing in drugs for neglected tropical diseases. He designed over 1,000 compounds that could inhibit HAT, but it was unclear whether the compounds would possess ADME properties sufficient to ensure good in vivo exposure. BVGH connected Dr. Pollastri with AstraZeneca, who agreed to test compounds from the Northeastern optimization efforts in their TIER1 ADME assays.
KCCR and Northeastern University researchers explored grant opportunities together, developed exchange between students, and conducted collaborative lab projects.
University of Mauritius, Northeastern University, and Emory University researchers collaborated to assess the efficacy of tuberculosis drugs using different delivery strategies.
Phosphodiesterases (PDEs) are important regulators of cell signal transduction, and PDE inhibitors have been developed to treat various diseases, such as erectile dysfunction and chronic obstructive pulmonary disease (COPD). After reading reports that PDE inhibition in T. brucei, which causes HAT, led to parasite death, Dr. Pollastri and colleagues screened existing human PDE inhibitors for activity against T. brucei PDEs. When the team examined the inhibitors’ structure-activity relationships (SAR) — correlations between compound structures and activity against parasite PDEs —, it was difficult to discern clear trends or patterns, which slowed the compound optimization process significantly. BVGH connected Dr. Pollastri with scientists at Eisai who had experience working with PDE inhibitors. The scientists provided Dr. Pollastri with valuable advice on compound optimization, including suggestions for future approaches and experiments.