by Sage Wesenberg, Biochemistry, 2019
After spending a decade in the pharmaceutical industry, Chemistry Professor and Interim Department Chair Michael Pollastri came to Northeastern to focus on finding cures for neglected tropical diseases. Recently, the National Institutes of Health (NIH) awarded him a $2.6 million grant to continue his work in drug discovery for human African trypanosomiasis (HAT), commonly called sleeping sickness. This grant will be a huge step toward furthering his preclinical research program that focuses on finding drug analogs to combat this deadly disease, with minimal side effects.
Sleeping sickness is an insect-borne, parasitic disease found in sub-Saharan Africa. The disease is transmitted by the tsetse fly, which are large flies (similar to a horsefly) that live off of vertebrate animal blood, including humans. Sleeping sickness starts off as a bloodstream infection, presenting itself in flu-like symptoms. However, the parasite then moves to the central nervous system and begins to cause more damage, causing the trademark symptoms of interrupting or reversing the sleep cycle. This eventually leads to a coma, and ultimately death. Currently, the drugs being used to treat the sleeping sickness are very toxic. One drug contains arsenic and kills 1 in 20 people who are treated with it. Those who survive this drug treatment often suffer brain damage. The second treatment is a cancer drug that requires an intense, multi-week intravenous regimen.
Pollastri’s passion for neglected disease research stems from the alarming fact that people living in poverty have minimal treatment options for deadly diseases, such as sleeping sickness. “To me, it seems like the right thing to do to focus on the poorest of the poor who have no one fighting for them,” said Pollastri. “I can take the skills I learned in the pharmaceutical industry and apply them to finding treatments for diseases that affect the poorest populations of the world. It may not be necessarily difficult to find the drugs we need, but relatively few have put time and attention into it.”
As part of this most recent grant, Pollastri will collaborate with Prof. Kojo Mensa-Wilmot from the University of Georgia. The team will repurpose existing drugs, such as cancer drugs, and re-optimize them to attack parasitic agents instead of cancer agents. This technique will provide a starting point for discovering new drugs to help form analogs that will fight the parasitic infection, and minimize other drug effects that can harm the body. With the University of Georgia and assistance from AstraZeneca, the research has made excellent progress. Pollastri credits this to the important collaborations they have formed. “This combination of academic and industrial drug discovery expertise provides a powerful research engine for neglected diseases.”
With this new grant, Pollastri’s lab will be able to take big steps forward in creating both potent and safe analogs to fight sleeping sickness. It will help Pollastri and his collaborators get the compounds through proof-of-concept experiments, where they will hopefully be shown to be safe in animals. These results can then be presented to organizations such as the Drugs for Neglected Diseases initiative, in the hopes that these compounds can be advanced toward clinical trials.
“This new infusion of funding will not only make progress toward finding safe and effective drugs for sleeping sickness, it will also help drive our neglected disease drug discovery program at Northeastern,” Pollastri said. “What we learn from this project will help create the foundation needed to advance other parasite-related disease projects here at Northeastern and beyond. This is a big step forward for us.”