The active ingredient of Synspira’s SNSP113, an inhaled investigational treatment for chronic lung infections, demonstrated an ability to completely eliminate antibiotic-resistant Pseudomonas aeruginosa bacteria, a major cause of lung disease in cystic fibrosis (CF) patients, according to a study done in the laboratory.
These latest findings, together with its proven ability to kill other dangerous bacteria that affect CF patients, make SNSP113 a possible game-changer for the treatment of chronic lung infections in these patients.
The study, “Novel Glycopolymer Eradicates Antibiotic- and CCCP-Induced Persister Cells in Pseudomonas aeruginosa,” was published in the journal Frontiers in Microbiology.
Recurrent lung infections in CF patients are often due to a subpopulation of drug-resistant bacteria known as persisters. Persisters are a major source of chronic, intractable lung infections because these slow-growing bacteria normally are not affected by antibiotics.
To determine the antibacterial effect of the active component of SNSP113, a complex sugar polymer called PAAG (polycationic glycopolymerpoly acetyl arginyl glucosamine), researchers simulated the natural formation of persisters by two methods: exposing Pseudomonas to commonly used antibiotics, or exposing them to a compound called carbonyl cyanide m-chlorophenylhydrazone (CCCP).
Strikingly, treatment with PAAG was able to rapidly kill both types of induced antibiotic-resistant P. aeruginosa.
When exposed to PAAG, antibiotic-tolerant P. aeruginosa bacteria numbers were 1 million to 10 million times lower within two to four hours, and the bacteria were completely eliminated within 24 hours.
PAAG was also more effective at eliminating CCCP-induced persister bacteria than antibiotics currently used to treat chronic infections, such as tobramycin, aztreonam, and macrolides. Complete eradication of CCCP-induced persister bacteria was seen within 24 hours after treatment.
Importantly, PAAG was able to eliminate P. aeruginosa persisters at concentrations not toxic to human lung cells grown in the lab.
The strong killing activity of the compound was linked to its capacity to disrupt the cell membrane of bacteria within minutes.
“There is a need for new target molecules with the ability to safely address persisters. These results provide evidence that PAAG rapidly permeabilizes and kills P. aeruginosa persister cells. In the in vitro studies, PAAG demonstrated bactericidal activity against antibiotic and CCCP-induced persister cells and was able to completely eradicate persisters,” Paul Orwin, PhD, professor of biology at California State University San Bernardino, said in a press release.
SNSP113 is gaining increased recognition as a very promising therapy to fight chronic lung infections. In recent months, the therapy was seen to boost the ability of antibiotics against Burkholderia cepacia and multidrug-resistant Staphylococcus aureus, two other bacteria that threaten CF patients.
Synspira successfully completed a Phase 1 trial (NCT03309358) evaluating the safety and tolerability of ascending doses of SNSP113 in healthy volunteers. The company plans to advance clinical studies in CF patients this year.
“Antibiotic-induced P. aeruginosa persisters are commonly implicated in relapsing and chronic lung infections, and increasingly recognized as culprits that outwit even the most aggressive therapies,” said Shenda Baker, PhD, CEO of Synspira. “We are optimistic that SNSP113 could provide a fundamentally different therapy for CF patients with chronic respiratory infections and may play a significant role in reducing antibiotic resistance.”