Up to $2.86M has been awarded to a research team including Penn State scientists to develop a new oral antibiotic to treat multidrug-resistant gonorrhea, a sexually transmitted disease caused by bacteria that have developed resistance to all but one existing antibiotic. The research team includes Penn State Professor of Biochemistry and Molecular Biology Kenneth Keiler, the U.S.-based clinical-stage biopharmaceutical company Microbiotix, as well as researchers from Emory University and the Uniformed Services University.
The funds are awarded by the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, CARB-X, a non-profit partnership dedicated to accelerating early stage antibacterial research and development to address the rising global threat of drug-resistant bacteria. If the project successfully achieves certain development milestones, the team will be eligible for an additional $16 million in funding from CARB-X.
"Drug-resistant gonorrhea is a growing global health problem that can cause serious and sometimes fatal health issues in men and woman and that has the possibility of increasing the risk of contracting or giving HIV," said Erin Duffy, chief of research and development at CARB-X, which is based at Boston University School of Law. "Neisseria gonorrhoeae has developed resistance to the effects of antibiotics, and in some cases, there is only one drug to which the bacteria are susceptible."
The World Health Organization (WHO) estimates that about 78 million people a year are infected with gonorrhea; roughly 1.14 million of those infections occur in the U.S., of which an estimated 550,000 involve drug-resistant bacteria. Drug-resistant N. gonorrhoeae is identified by the WHO as a 'priority' pathogen, and classified by the U.S. Centers for Disease Control and Prevention (CDC) as an 'urgent public health threat' that requires aggressive action.
This project features a novel approach to creating a new antibiotic and is in the early stages of development. If successful and approved for use in patients, it could represent tremendous progress in the treatment of gonorrhea and help curb the spread of drug-resistant bacteria."
Erin Duffy, chief of research and development at CARB-X
The research team will optimize and develop a series of compounds into a novel antibiotic that targets and inhibits an essential pathway for the bacteria to grow and replicate--the trans-translation pathway. This pathway rescues ribosomes that become trapped because of errors in protein synthesis.
"Because the trans-translation pathway is not found in animals, inhibiting the pathway should have a specific effect on bacteria and not host cells," said Keiler. "This specificity makes inhibition of the trans-translation an attractive strategy for creating novel antibacterial agents."
Keiler discovered the trans-translation system as a graduate student, and his lab has studied the pathway over the last two decades. They have studied the biochemistry of the pathway and identified and characterized lead compounds for potential future drugs.
"This grant is the culmination of a lab-to-clinic odyssey that started about 16 years ago with a seed grant from what is now the Penn State Huck Institutes of the Life Sciences and seed funding from the Eberly College of Science," said Keiler.
For this grant, Keiler's lab will conduct biochemical experiments to test the activity of new compounds and microbiological characterization of the drugs, while Microbiotix and other collaborators will focus on drug formulation, animal studies, and, if successful, Phase I clinical trials in humans.
"Proposed as a single dose oral therapy, this innovative program has great potential, not only to address the urgent threat posed by multidrug-resistant N. gonorrhoeae, but also to address other sexually-transmitted infection (STI) pathogens commonly found as coinfections," said Terry Bowlin, president & CEO of Microbiotix.
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