Treatment for Drug Resistant Bacterial Infections
AB569 is a new drug candidate for treating antibiotic resistant bacterial infections, primarily in the lungs. It also has potential to be modified for use in other indications, including adaptation as a topical cream for bacterial skin infections.
AB569 has a mechanism of action that differs from the mechanism of action of antibiotics. AB569 has orphan drug status from the U.S. FDA for the treatment of Pseudomonas aeruginosa infections in the respiratory tracts of patients with cystic fibrosis. AB569 has orphan medicinal product designation from the European Medicines Agency for the treatment of cystic fibrosis.
In December 2021 Arch Biopartners announced that Dr. Daniel Hassett, Professor at the University of Cincinnati College of Medicine – leading the AB569 team at Arch, published a paper entitled “AB569, a Novel, Topical Bactericidal Gel Formulation, Kills Pseudomonas aeruginosa and Promotes Wound Healing in a Murine Model of Burn Wound Infection” in the journal Infection and Immunity.
In the publication we first show that AB569 acts synergistically to kill all human burn wound strains of P. aeruginosa in vitro. This was found to be due, in part, to the generation of A-NO2–-mediated nitric oxide (NO) formation coupled with the metal chelating properties of Na2-EDTA. Using a murine scald burn wound model of P. aeruginosa infection, an AB569-Solosite gel formulation eradicated all bacteria. Futher, we also demonstrate enhanced AB569-mediated wound healing by not only accelerating wound contraction, but also by reducing levels of the proinflammatory cytokines interleukin-6 (IL-6) and IL-1β while increasing the levels of anti-inflammatory cytokine, IL-10, and granulocyte-colony-stimulating factor (G-CSF).
In March 2021, Dr. Hassett, also published a paper entitled “AB569, A Non-toxic Combination of Acidified Nitrite and EDTA, is Effective at Killing the Notorious Iraq/Afghanistan Combat Wound Pathogens, Multi-Drug Resistant Acinetobacter baumannii and Acinetobacter spp.” in the journal PloS One.
Dr. Hassett, who collaborated with both the United States Air Force and Arch, demonstrated that AB569 kills multi-drug resistant strains of Acinetobacter baumannii and Acinetobacter spp. bacteria. These pathogens have been shown to infect soldiers who are injured by gun, shrapnel, burn or blast wounds.
Multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Acinetobacter spp. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO2-) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all Ab and Acinetobacter spp. strains, respectively.
Arch is currently exploring new opportunities to sponsor a human trial to prevent, treat, and heal wound infections using an AB569 topical cream or gel. Similar clinical opportunities to test the AB569 wound cream exist in targeting abscesses, diabetic wounds and skin ulcers.
Future clinical developments may also involve using AB569 for problematic infections involving the urinary tract as well as bacterial lung infections that are a hallmark of Cystic Fibrosis and chronic obstructive pulmonary disease (COPD) airway disease.
AB569 and Respiratory Pseudomonas Aeruginosa Infections
Two deadly diseases, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), are exacerbated by airway bacterial infections that significantly impact the overall quality of patient’s lives. There are approximately 40,000 CF patients and over 14 million individuals diagnosed with COPD in the United States. In both diseases, antibiotic resistant Gram-negative bacteria, such as Pseudomonas aeruginosa (P. aeruginosa), often constitute a significant and problematic cause of the pulmonary exacerbations that result in frequent hospitalizations of these patients.
AB569 is a synergistic antimicrobial tandem of slightly acidified sodium nitrite and EDTA that has the critical advantage over conventional antibiotics in that it down regulates many of the genes in the bacterium responsible for survival. In a recent publication in the prestigious Proceedings of the National Academy of Sciences (abstract – PNAS March 3, 2020), Dr. Hassett’s group showed that AB569 caused a catastrophic loss of the capacity to support vital core biosynthetic and metabolic pathways of another multi-drug resistant pathogen, Pseudomonas aeruginosa. These include the synthesis of DNA, RNA, protein, ATP and the ability of bacteria to breathe by both aerobic and anaerobic respiration.