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New hope for drug discovery in African sleeping sickness

Date:
October 25, 2014
Source:
Northeastern University
Summary:
African sleeping sickness, the neglected trop­ical dis­ease, affects tens of thou­sands of people and is mostly fatal. Now, new research has iden­ti­fied hun­dreds of chem­ical com­pounds that could lead to a cure.
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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 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.


Story Source:

Materials provided by Northeastern University. Original written by Joe O'Connell. Note: Content may be edited for style and length.


Journal Reference:

  1. Rosario Diaz, Sandra A. Luengo-Arratta, João D. Seixas, Emanuele Amata, William Devine, Carlos Cordon-Obras, Domingo I. Rojas-Barros, Elena Jimenez, Fatima Ortega, Sabrinia Crouch, Gonzalo Colmenarejo, Jose Maria Fiandor, Jose Julio Martin, Manuela Berlanga, Silvia Gonzalez, Pilar Manzano, Miguel Navarro, Michael P. Pollastri. Identification and Characterization of Hundreds of Potent and Selective Inhibitors of Trypanosoma brucei Growth from a Kinase-Targeted Library Screening Campaign. PLoS Neglected Tropical Diseases, 2014; 8 (10): e3253 DOI: 10.1371/journal.pntd.0003253

Cite This Page:

Northeastern University. "New hope for drug discovery in African sleeping sickness." ScienceDaily. ScienceDaily, 25 October 2014. <www.sciencedaily.com/releases/2014/10/141025152704.htm>.
Northeastern University. (2014, October 25). New hope for drug discovery in African sleeping sickness. ScienceDaily. Retrieved May 29, 2024 from www.sciencedaily.com/releases/2014/10/141025152704.htm
Northeastern University. "New hope for drug discovery in African sleeping sickness." ScienceDaily. www.sciencedaily.com/releases/2014/10/141025152704.htm (accessed May 29, 2024).

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