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Encouraging Development of Therapeutics for Neglected Diseases - Day 2


Day 1  |  Day 2

 

TUESDAY, MARCH 13

7:30 am Morning Coffee


8:35 Chairperson’s Opening Remarks
Aris Persidis, Ph.D., President, Biovista, Inc.

8:40 Repurposing Kinase-Targeted Medicinal Chemistry for Neglected Tropical Disease Drug Discovery

Mike Pollastri, Ph.D., Associate Professor, Chemistry & Chemical Biology, Northeastern University

This presentation will discuss the target purposing approach for neglected disease drug discovery, highlighted by some examples in my lab where we have found anti-parasitic activities in classes of human kinase inhibitors.

9:10 Synopsis of Breakout Discussions

Sponsored by
Biovista

9:30 Systematic Drug Repositioning for Neglected Diseases and Not Only

Aris Persidis, Ph.D., President, Biovista, Inc.
Drug repositioning is emerging as a major strategy to accelerate the development of drugs in rare or neglected diseases and beyond. The potential for innovation and novelty is significant and a number of case studies will be discussed, including Friedrich's Ataxia, Leber's neuropathy, progressive multiple sclerosis and others.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:40 Drug Repositioning: An Opportunistic Approach to Identifying New Drugs for Malaria?

Julie Lotharius, Ph.D., Associate Director, Translational Medicine, Medicines for Malaria Venture

Medicines for Malaria Venture has tested a vast number of approved, investigational and discontinued drugs in an in vitro assay of human Plasmodium falciparum blood stage infection. Several several hits with low micromolar activity and acceptable human safety and pharmacokinetic profiles were then followed up by in vivo testing in a humanized mouse model of P falciparum infection. In addition, target and genome-based searches comparing the mechanism of action of known drugs to pathways responsible for parasite survival and propagation have been employed to identify compounds from the clinical development pipeline that may have anti-malarial activity. Data generated from these activities will be presented.

11:10 Repurposing Drug Candidates - Fexinidazole as a Promising Treatment for Visceral Leishmaniasis

Susan Wyllie, Senior Research Associate and Lecturer, Division of Biological Chemistry and Drug Discovery, University of Dundee

We report the potential for therapeutic switching of fexinidazole, currently in phase I clinical trials for treatment of human African trypanosomiasis, as a novel oral treatment for Visceral Leishmaniasis. This 2-substituted 5-nitroimidazole is rapidly oxidized in vivo to sulfoxide and sulfone metabolites. These metabolites were both active against Leishmania donovani amastigotes grown in macrophages, whereas fexinidazole itself is inactive. A once daily regimen for 5 days at 200mg kg-1 caused a 98.4% suppression of infection in a VL mouse model, superior to the clinical drugs miltefosine or pentostam. In African trypanosomes, the mode of action of nitrodrugs involves reductive activation via an NADH-dependent bacterial-like nitroreductase. Overexpression of the the leishmania homologue in L. donovani increased sensitivity to fexinidazole by 19-fold indicating that a similar mechanism is involved in these parasites. These findings illustrate the potential of fexinidazole as a much needed oral treatment for VL.

11:40 Repurposing Drugs for Tropical Diseases: Case Studies and Open-source Screening Initiatives

Curtis R. Chong, M.D., Ph.D., M.Phil., Partners Cancer Care Hematology & Oncology Fellow, Dana Farber, Brigham and Women’s Hospital, Massachusetts General Hospital

12:10 pm End of Conference

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