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Synspira’s glycopolymer fights antibiotic resistance
CAMBRIDGE, Mass.—Yesterday Synspira, a company developing a new class of inhaled glycopolymer-based therapeutics for the treatment of pulmonary disease, announced the publication of a study exploring poly-N (acetyl, arginyl) glucosamine (PAAG) as a potential new treatment for methicillin-resistant Staphylococcus aureus (MRSA). The full paper, “In Vitro Activity of Novel Glycopolymer Against Clinical Isolates of Multidrug-Resistant Staphylococcus aureus,” is published in PLOS ONE.
MRSA is a contagious bacterial infection resistant to numerous antibiotics, making it increasingly challenging to treat. The prevalence of MRSA in patients with cystic fibrosis (CF) is increasing steadily and is a significant contributor to pulmonary decline.
Synspira is developing PAAG as part of its new class of glycopolymers to serve as an adjunctive therapy to traditional antibiotic strategies to treat MRSA and multidrug-resistant (MDR) infections. The results of the study demonstrate the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus (S. aureus) and its ability to dramatically reduce the amount of antibiotic required to kill the bacteria.
“The study published [yesterday] explores how PAAG can enhance the efficacy of current antibiotics used to treat MRSA, a common pathogen in patients with cystic fibrosis, who face frequent complications from MDR bacteria,” said Shenda Baker, Ph.D., Chief Executive Officer, Synspira. “PAAG is the active component in Synspira’s inhaled pulmonary candidate, SNSP113, which is currently in a Phase 1 clinical trial for the treatment of CF.”
SNSP113 is a glycopolymer-based therapeutic developed as an inhaled treatment to improve lung function in patients with cystic fibrosis. As a modified polysaccharide molecule, SNSP113 interacts with structural polymers in protective bacterial biofilms, breaking them apart, and with native glycoproteins in mucus, reducing mucus viscosity and adhesion.
SNSP113 also interacts with the cell walls of invading bacteria by increasing their permeability, thereby reducing their inherent viability and potentiating the efficacy of antibiotics. SNSP113 is designed to reduce infection and inflammation, the key drivers of pulmonary exacerbations and pulmonary decline in CF patients.
“Mupirocin, oxacillin, and bacitracin have been used as topical agents or intranasal treatments to prevent onset and spread of primary and secondary MRSA infections for over 10 years,” the study text says. “However, extensive use of mupirocin, bacitracin and oxacillin has also culminated in increased resistance in MRSA strains, which is also consistently reported in community-associated MRSA infections. Studies and clinical trials have also focused on antimicrobial peptides for their wide-spectrum of antibacterial activity. However, many antimicrobial peptides are polycationic and have some cytotoxicity, limiting their use.
“Mupirocin and bacitracin were selected as comparators as they have very different mechanisms of action. Bacitracin disrupts Gram-positive bacteria by interfering with cell wall synthesis and is used topically. Mupirocin selectively binds to bacterial isoleucyl-tRNA synthetase, which stops or slows bacterial protein synthesis. Also, mupirocin is known to have genetic transfer of resistance and bacitracin is known to develop resistance slowly, compared to other conventional antibiotics,” the study continues.
The recently published study showed antibacterial efficacy of PAAG against clinical isolates of MRSA and mupirocin resistant S. aureus. These results demonstrate that PAAG rapidly permeabilizes the bacteria to both directly kill MRSA and is synergistic with antibiotics, reducing the minimum inhibitory concentration below levels where bacteria are considered resistant and resensitizing bacteria to the antibiotic. In addition, in a prior study published in PLOS ONE, PAAG improved the effectiveness of antibiotics against Burkholderia cepacia complex.
“This new class of glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria,” stated John Uhrig, Postdoctoral Fellow at the Division of Infectious Disease at the Medical College of Wisconsin. “PAAG’s ability to permeabilize bacteria reduces their ability to respond to a variety of antibiotic challenges, and thus has tremendous potential for treating MDR infections.”
“The findings of the current study point to the potential of PAAG as a means to treat MRSA infections through a direct bactericidal activity or through combination therapies. PAAG was observed to enhance the antibacterial activity of oxacillin, potentially increasing its clinical efficacy. PAAG was also shown to re-sensitize a resistant strain of S. aureus to both mupirocin and bacitracin, suggesting that PAAG could potentially expand the range of multidrug-resistant bacteria that can be treated, should these observations continue for a broader range of bacteria,” notes the study.
The study was conducted by Synedgen, a pioneering biotechnology company using the science of glycomics to discover and develop polysaccharide-based drugs that enhance and mimic the innate immune system. Synspira has an exclusive license from Synedgen to the Glycomics Technology Platform for the development of inhaled therapeutics in pulmonary indications.