Neglected Tropical Diseases: Research Bites Back

Progress toward the treatment of three major parasitic diseases (sleeping sickness, Chagas disease, and leishmaniasis) was recently demonstrated in an article published online last month in the journal Nature (August 8, 2016). Collectively, these three diseases affect 20million people per year, resulting in 50 thousand deaths. Researchers were able to identify and optimize a small molecule that selectively inhibited the parasite proteasomes, and yet did not inhibit human proteasomes. This gives some hope that with further development, the drug may effectively treat those infected with these parasites without having toxic effects on the patients. These three diseases are known to be caused by genetically similar kinetoplastid parasites, and are part of a larger group of what are referred to as neglected tropical diseases (NTDs). Researchers discovered this promising new compound by screening a library of 3 million small molecules, and found that mice given the optimized drug were able to effectively clear the parasites in preclinical infectionmodels. Althoughwe are still a longway from seeing this drug applied in the clinic, the idea that a single drug could have such broadspectrum activity against three highly prevalent NTDs is encouraging– particularly since the available treatments for these diseases are not well tolerated and/or easily administered. NTDs are a diverse group of more than a dozen diseases that collectively affect more than a billion people–mostly the poor–primarily in developing countries with limited resources. Other NTDs include (but are not limited to) schistosomiasis, lymphatic filariasis (elephantiasis), onchocerciasis (river blindness), trachoma, dengue and rabies, as well as helminth-related diseases such as roundworm, whipworm, and hookworm. In 2012, the World Health Organization issued a strategic road map for elimination and/or effective control for many of these NTDs by 2020. This goal has been backed with resources and financial support in collective efforts from major pharmaceutical companies, non-profit agencies such as the Gates Foundation, PATH, and the Drugs for Neglected Diseases Initiative, as well as several academic and governmental agencies. This massive, collaborative effort is of the scale and breadth needed to tackle such as huge undertaking, and the goal is not insurmountable. Treatments for several NTDs are in fact already available, yet will need proper infrastructure for distribution as well as accurate testing and epidemiological analyses for effective implementation and monitoring. Vector and non-human host identification and control, clean water access, and other hygiene and sanitation methodsmust also be implemented effectively to reach this goal. In addition to thesewell-defined strategic goals, the complex goals of identifying new treatments and vaccines are likely to require amore in-depth investment of time and resources. As alluded to above, one reason targeted proteasome inhibition is so exciting as a treatment approach is that the available treatments for