Synspira’s Novel Glycopolymer Improves Effectiveness of Antibiotics Against Drug-resistant Bacteria Associated with Cystic Fibrosis
Synspira, a privately held company developing a new class of inhaled glycopolymer-based therapeutics for the treatment of pulmonary disease, today announced the results of a combination study leveraging polycationic glycopolymers and conventional antibiotics as a potential treatment for pulmonary infection caused by the Burkholderia cepacia complex (Bcc) in patients with cystic fibrosis. The publication, “Novel glycopolymer sensitizes Burkholderia cepacia complex isolates from cystic fibrosis patients to tobramycin and meropenem” is published in PLOS ONE.
“The results published in PLOS ONE demonstrate that our inhaled glycopolymer drug candidate, PAAG, has the potential to significantly enhance the activity of antibiotics that are used for the treatment of lung infections caused by Burkholderia cepacia complex, a relatively uncommon but often fatal infection in cystic fibrosis,” said Synspira CEO, Shenda Baker, Ph.D. “By breaking down the outer membrane of the bacteria, PAAG makes bacteria more susceptible to antibiotics, even in species that were previously resistant to antibiotic therapy. We believe that our formulated drug SNSP113 using PAAG has the potential to address a key unmet need in these types of infections and to be a new approach to the growing problem of antibiotic resistance in pulmonary indications.”
Chronic pulmonary infection is a characteristic of lung disease in patients with cystic fibrosis (CF). Infections caused by Bcc are particularly difficult to treat because the complex consists of a variety of related strains of bacteria with variable sensitivities to antibiotics, and these strains are naturally multidrug resistant to many common antibiotics. Bcc can acquire resistance easily, making eradication from the lungs of CF patients virtually impossible and leaving patients with few effective therapies. Chronic infection results in progressive loss of lung function, and Bcc is known for its lethality in CF patients.
Synspira is developing a new class of direct-acting glycopolymers, PAAG, as an alternative to traditional antibiotic strategies with lead candidate, SNSP113. The results published in PLOS ONEdemonstrate that PAAG rapidly targets bacterial outer membranes and permeabilizes them upon contact, facilitating the potentiation, or enhancement, of antibiotic activity when used in combination with meropenem and tobramycin. The results show that this combination therapy is more effective than combinations with ceftazidime against all Bcc strains and thus has the potential to treat lung infections caused by Bcc in CF patients.
“Unfortunately, Burkholderia cepacia complex infections are some of the most difficult to treat infections among persons with cystic fibrosis and can result in permanent loss of pulmonary function and early death,” said John LiPuma, M.D., Department of Pediatrics and Communicable Diseases, University of Michigan Medical School. “There is a tremendous need for agents that can actively target Bcc and improve patient outcomes”.
In the study, antibiotic synergy was observed with tobramycin and meropenem when used in combination treatment with PAAG. The results demonstrate the ability of PAAG to reduce the Minimum Inhibitory Concentration (MIC) of tobramycin and meropenem below their Clinical and Laboratory Standards Institute (CLSI) breakpoints, making them effective in a clinically acceptable dosage range. Ceftazidime was unable to enhance the activity of tobramycin and meropenem.
Combinations of tobramycin and meropenem, and often with ceftazidime, can be used to treat Bcc infections in CF. Though these antimicrobial agents can cause a reduction in bacterial density, they have shown limited improvement in lung function in CF patients with Bcc, likely because of the diversity of Bcc strains to which they have variable efficacy. PAAG demonstrates broad antibacterial activity across a broad spectrum of drug resistant Bcc and shows synergy with antibiotics in vitro, suggesting its potential for use as a novel therapeutic strategy against highly resistant bacterial infections.
SNSP113 is a glycopolymer-based therapeutic being developed as an inhaled treatment to improve lung function in patients with cystic fibrosis. As a modified polysaccharide molecule, SNSP113 interacts with polysaccharides in protective bacterial biofilms, breaking them apart, and with native glycoproteins in mucus, reducing mucus viscosity and adhesion. Both biofilms and mucus are key drivers of pulmonary exacerbations and infections in cystic fibrosis patients. SNSP113 also interacts with the cell walls of invading bacteria increasing their permeability, thereby reducing their inherent viability and potentiating the efficacy of antibiotics.
Synspira is developing a new class of inhalable glycopolymer-based therapeutics that disrupt mucus accumulation and biofilm invasion, which are key drivers of pulmonary diseases including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and pneumonia. Synspira has an exclusive license from Synedgen to the Glycomics Technology Platform for the development of inhaled glycopolymer-based therapeutics in pulmonary indications. Synspira is using proprietary modified polysaccharide molecules to disrupt bacterial biofilms and to help expectorate mucus, exposing otherwise protected bacteria to antibiotics. This new approach to the treatment of disease pathology has the potential to improve pulmonary function and reduce antibiotic resistance in a number of infectious diseases. www.synspira.com