For this collaboration, Kenneth Keiler, professor of biochemistry and molecular biology and principal investigator on the project, and his team will screen “orphan” drug compounds that were identified by TB Alliance, a nonprofit organization dedicated to developing better tuberculosis drugs, and GSK, a global healthcare company. These orphan compounds had been developed to fight other diseases and did not work for their original purpose. Now Keiler aims to discover if they may be viable to be made into effective tuberculosis drugs.
Keiler’s team was chosen for this collaboration because of his work discovering “trans-translation,” a process in bacteria that ensures protein synthesis is not interrupted. Keiler believes disrupting the trans-translation process is key to stopping the growth of bacterial diseases like tuberculosis.
Tuberculosis affects two billion people worldwide and can be found in every country in the world. However, the impact of tuberculosis is felt most strongly in resource-poor nations where patients might not have access to both the medication or regular medical oversight to ensure effective treatment of tuberculosis. “Without constant monitoring, people tend to stop taking the drugs,” said Keiler.
Even in the U.S., compliance with taking the full course of tuberculosis medication can be a problem, leading to drug-resistant strains of tuberculosis. Part of this is due to the length of treatment time for the disease, said Keiler. Current treatment for tuberculosis involves a cocktail of antibiotics that must be taken for at least six months (but as long as two years) to be effective. Keiler’s end goal with this research is to be able to shorten the treatment from six months to two weeks using antibiotics made from molecules that disrupt trans-translation.
So far, Keiler’s team has identified three families of compounds donated from GSK that could be very promising for new tuberculosis drug development.
“We identified several compounds that inhibit the protein quality control pathway that we study,” said Keiler. “We have also learned some important basic science about the quality control pathway from the activity of the molecules.”
Keiler’s team is currently finishing the molecular experiments and further testing for drug development is planned.