Researchers identify compounds that could lead to discovery of new drugs for African sleeping sickness

Northeastern UniversityOct 27 2014

Targeting chemical compounds that could lead to a cure

In early drug discovery, you need a starting point, says North­eastern Uni­ver­sity asso­ciate pro­fessor of chem­istry and chemical biology Michael Pollastri.

In a new research paper published Thursday in the journal PLOS Neglected Tropical Diseases, Pollastri and his colleagues present hun­dreds of such starting points for poten­tially treating African sleeping sick­ness, a deadly disease that claims thousands of lives 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 African 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 African 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.

African 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.