In early drug dis颅covery, you need a starting point, says North颅eastern Uni颅ver颅sity asso颅ciate pro颅fessor of chem颅istry and chem颅ical biology Michael Pollastri.

In a new research paper pub颅lished Thursday in the journal PLOS-????Neglected Trop颅ical Dis颅eases, Pol颅lastri and his col颅leagues present hun颅dreds of such starting points for poten颅tially treating Human African try颅panoso颅mi颅asis, or sleeping sick颅ness, a deadly dis颅ease that affects thou颅sands of people annually.

Pol颅lastri, who runs Northeastern??s Lab颅o颅ra颅tory for Neglected Dis颅ease Drug Dis颅covery, and co-????collaborators at the Spanish National Research Council for Sci颅en颅tific Research worked with global health颅care com颅pany Glax颅o颅SmithK颅line to screen and test more than?42,000 chem颅ical com颅pounds against the par颅a颅sites that cause sleeping sick颅ness. In their paper, they report iden颅ti颅fying nearly 800 com颅pounds that rep颅re颅sent good options for early drug discovery.

??Having this many good starting points for dis颅covery of new drugs for sleeping sick颅ness is a big deal and could ulti颅mately lead to a cure,?? Pol颅lastri?said.

Pol颅lastri also high颅lighted another exciting com颅po颅nent to this project. Pre颅vi颅ously, he cre颅ated a data-????sharing portal where sci颅en颅tists and researchers can access and con颅tribute to each other??s work on neglected trop颅ical dis颅eases. This new research on sleeping sick颅ness will be the first data to be deposited on the portal, which was sup颅ported by a crowd颅funding cam颅paign.

??This is a venue where other people, par颅tic颅u颅larly med颅ical chemists from around the world, can con颅tribute to the project in one way or the other,?? Pol颅lastri?said.

Sleeping sick颅ness is one of the World Health Orga颅ni颅za颅tion??s 17 neglected trop颅ical dis颅eases. It is found only in sub-????Sahara Africa and infects between 10,000 and 30,000 people annu颅ally. Tsetse flies transmit the dis颅ease and symp颅toms come in two stages. In the first stage an infected person expe颅ri颅ences symp颅toms such as fever, headaches, joint pains, and itching. In the second stage, par颅a颅sites enter the person??s cen颅tral ner颅vous system and that leads to sleep cycle dis颅rup颅tion, coma and, if untreated, death.

??It is a nasty, nasty dis颅ease,?? said Pol颅lastri, adding that it hasn??t been widely researched and that even the cur颅rent drug treat颅ments are lengthy, toxic, and often fatal themselves.

Pol颅lastri and his co-????collaborators worked with Dr. Miguel Navarro at the Spanish National Research Council in Granada, Spain, and with GlaxoSmithKline??s OpenLab ini颅tia颅tive to run the screen颅ings, which focused on inhibitors that block the process of phos颅phoryl transfer medi颅ated by enzymes called kinases. This process is a key step in cel颅lular sig颅naling, and kinase inhibitors have been his颅tor颅i颅cally pur颅sued for poten颅tial treat颅ment of some can颅cers and inflam颅ma颅tory dis颅or颅ders, he explained.

The next step will involve con颅tinued testing on these promising 800 com颅pounds and deter颅mining which ones can be tweaked in order to have the right potency, prop颅er颅ties, and lack of tox颅i颅city to treat the dis颅ease, he said. At that point, they may be able to advance a com颅pound toward clin颅ical trials for sleeping sickness.