Respiratory Infection Candidate AB569 Kills Resistant Bacteria, Study Shows

Respiratory Infection Candidate AB569 Kills Resistant Bacteria, Study Shows
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AB569 is safe and effective at killing bacteria resistant to traditional antibiotics, in particular Pseudomonas aeruginosa (P. aeruginosa), an important disease-exacerbating microbe in cystic fibrosis (CF), a study showed.

The study, “AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria,” was published in the journal Proceedings of the National Academy of Sciences of the United States of America.

AB569, Arch Biopartners’ treatment candidate for bacterial infections in patients with CF, chronic obstructive pulmonary disease (COPD), and other respiratory diseases, previously received a U.S. patent, protecting its composition and granting the company exclusive commercial rights.

P. aeruginosa is the main bacterial agent involved in the onset and progression of CF lung disease, and is a key determinant of patients’ quality of life, hospitalizations, and life expectancy. These infections are very hard to treat, as the bacteria are highly resistant to traditional antibiotics.

AB569, developed by Daniel Hassett, PhD, a principal scientist at Arch and professor at the University of Cincinnati College Of Medicine, is a combination of acidified nitrite and disodium ethylenediaminetetraacetic acid. Both compounds, extensively used in medical settings, are approved by the U.S. Food and Drug Administration (FDA) and are believed to work together for a more potent bacteria-killing effect.

Researchers led by Hassett tested AB569 in human cell lines and found the agent was not toxic when used at the concentration needed to kill bacteria. The compound effectively killed P. aeruginosa biofilms, bacteria aggregates that act in a coordinated way to evade a host’s defenses and acquire resistance to treatments.

The team also tested higher doses of AB569 in a mouse model of P. aeruginosa chronic lung infection. The results again showed the potential therapy was effective and safe at targeting and killing these bacteria, highlighting its potential as a human therapeutic agent. These studies allowed researchers to hone in on how exactly the compound can neutralize and kill the resistant bacteria.

“Antibiotics affect specific processes in the bacteria, but not all of them. AB569 affects multiple processes at once, leaving the exposed bacteria simply overwhelmed,” Hasset said in a University of Cincinnati news story.

“AB569 kills these pathogenic [disease-causing] bacteria by targeting their DNA, RNA, and protein biosynthesis [production] as well as energy and iron metabolism at concentrations that do not harm human cells,” he added.

In living organisms, DNA molecules store genetic information, and RNA molecules are used as a template for the production of proteins.

Researchers also believe that AB569 can be an innovative method to address a series of other opportunistic infections, including those caused by so-called superbugs — microbes that are resistant to several antibiotics (multidrug resistance) and are among major threats to global human health.

P. aeruginosa is among a group of pathogens called ESKAPE pathogens, which are the most resistant and dangerous to humans.

The therapy received orphan drug status from the FDA for the treatment of CF patients infected with P. aeruginosa, and orphan medicinal product designation from the European Medicines Agency (EMA).

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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