The compound has been licensed to Arch Biopartners and is currently in Phase I clinical trials.
Late last year, the U.S. Centers for Disease Control and Prevention (CDC) issued a new report about the threat of antibiotic-resistant bacteria, which showed more than 2.8 million antibiotic-resistant infections each year, killing more than 35,000 people. Although we are making headway in this area, there is still a need for effective antibiotics for the toughest superbugs.
Researchers at Simon Fraser University in Burnaby, British Columbia, Canada, in collaboration with researchers at the University of Cincinnati, have developed a new compound, AB569, that is effective in killing disease-causing bacteria without doing damage to human cells. The compound has been licensed to Toronto, Ontario-based Arch Biopartners and is currently in Phase I clinical trials.
The researchers, led by Daniel Hassett at the University of Cincinnati, where the drug was developed, published the results of an efficacy study of AB569 in the Proceedings of the National Academy of Sciences of the United States (PNAS).
“We have a growing crisis with antibiotics becoming less and less effective, and treatments are failing,” said SFU’s Geoff Winsor, lead database developer in the laboratory of SFU professor Fiona Brinkman, who is leading the work at SFU. “That’s why it’s important to test and develop new drugs and approaches to treat disease-causing bacteria that are highly resistant to existing antibiotics.”
AB569 contains two inexpensive chemicals, ethylenediaminetetraacetic acid (EDTA) and acidified nitrite. The SFU team analyzed the chemicals at the molecular level to determine how they worked together to kill drug-resistant Pseudomonas aeruginosa, leveraging their Pseudomonas Genome Database and computer-based analyses of molecular data.
P. aeruginosa can cause pneumonia, urinary tract infections and blood infections. It is the top cause of death in patients with cystic fibrosis (CF). Hospitalized patients or immune-compromised patients are at particularly high risk from the bacteria, which is classified by the World Health Organization as a “priority pathogen” of concern.
The top three priority pathogens include Acinetobacter baumannii, P. aeruginosa, and Enterobacteriaceae. AB569 has demonstrated the ability to kill all three.
The authors wrote, “Our data implicate that AB569 is a safe and effective means to kill pathogenic bacteria, suggesting that simple strategies could be applied with highly advantageous therapeutic/toxicity index ratios to pathogens associated with a myriad of periepithelial infections and related disease scenarios.”
Their study indicates that the compound causes a significant loss of the bacteria’s ability to support core pathways that include DNA, RNA, protein, ATP biosynthesis, and iron metabolism. One possible mechanism it works is by producing more stable SNO proteins, which are involved in numerous signaling pathways.
“AB569 kills these pathogen bacteria by targeting their DNA, RNA and protein biosynthesis as well as energy and iron metabolism in bacteria at concentrations that do not harm human cells,” said Hassett. “Our data implicate that AB569 is a safe and effective means that could be applied to eradicate these superbugs.”
He added, “These superbugs have an ingenious mechanism of being able to resist traditional antibiotic therapies by a vast number of acquired strategies. Antibiotics affect specific processes in the bacteria, but not all of them. AB569 affects multiple processes at once leaving the exposed bacteria simply overwhelmed.”
Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted AB569 orphan drug designation.
