New hope for drug discovery in African sleeping sickness

In a new research paper pub­lished in the journal PLOS-​​Neglected Trop­ical Dis­eases, Pol­lastri and his col­leagues present hun­dreds of such starting points for poten­tially treating Human African try­panoso­mi­asis, or sleeping sick­ness, a deadly dis­ease that affects thou­sands of people annually.

Pol­lastri, who runs Northeastern's Lab­o­ra­tory for Neglected Dis­ease Drug Dis­covery, and co-​​collaborators at the Spanish National Research Council for Sci­en­tific Research worked with global health­care com­pany Glax­o­SmithK­line to screen and test more than 42,000 chem­ical com­pounds against the par­a­sites that cause sleeping sick­ness. In their paper, they report iden­ti­fying nearly 800 com­pounds that rep­re­sent good options for early drug discovery.

"Having this many good starting points for dis­covery of new drugs for sleeping sick­ness is a big deal and could ulti­mately lead to a cure," Pol­lastri said.

Pol­lastri also high­lighted another exciting com­po­nent to this project. Pre­vi­ously, he cre­ated a data-​​sharing portal where sci­en­tists and researchers can access and con­tribute to each other's work on neglected trop­ical dis­eases. This new research on sleeping sick­ness will be the first data to be deposited on the portal, which was sup­ported by a crowd­funding cam­paign.

"This is a venue where other people, par­tic­u­larly med­ical chemists from around the world, can con­tribute to the project in one way or the other," Pol­lastri said.

Sleeping sick­ness is one of the World Health Orga­ni­za­tion's 17 neglected trop­ical dis­eases. It is found only in sub-​​Sahara Africa and infects between 10,000 and 30,000 people annu­ally. Tsetse flies transmit the dis­ease and symp­toms come in two stages. In the first stage an infected person expe­ri­ences symp­toms such as fever, headaches, joint pains, and itching. In the second stage, par­a­sites enter the person's cen­tral ner­vous system and that leads to sleep cycle dis­rup­tion, coma and, if untreated, death.

"It is a nasty, nasty dis­ease," said Pol­lastri, adding that it hasn't been widely researched and that even the cur­rent drug treat­ments are lengthy, toxic, and often fatal themselves.

Pol­lastri and his co-​​collaborators worked with Dr. Miguel Navarro at the Spanish National Research Council in Granada, Spain, and with GlaxoSmithKline's OpenLab ini­tia­tive to run the screen­ings, which focused on inhibitors that block the process of phos­phoryl transfer medi­ated by enzymes called kinases. This process is a key step in cel­lular sig­naling, and kinase inhibitors have been his­tor­i­cally pur­sued for poten­tial treat­ment of some can­cers and inflam­ma­tory dis­or­ders, he explained.

The next step will involve con­tinued testing on these promising 800 com­pounds and deter­mining which ones can be tweaked in order to have the right potency, prop­er­ties, and lack of tox­i­city to treat the dis­ease, he said. At that point, they may be able to advance a com­pound toward clin­ical trials for sleeping sickness.