Tackling Antibiotic-resistance: Nitric Oxide-based Treatments for Respiratory Diseases
Nitric oxide plays a crucial role in many physiological processes in the human body, including our immune system’s response to pathogens. The failure of conventional antibiotics to treat numerous antibiotic-resistant infections necessitates the development of new agents – as a natural anti-microbial nitric oxide holds particular promise. To learn more about the power of nitric oxide as a means for treating numerous diseases, including respiratory infections, we spoke to Mark Schoenfisch, PhD, President and Chief Scientific Officer at Vast Therapeutics.
Q: Could you provide us with an overview of Vast Therapeutics?
A: Vast Therapeutics is an innovative, preclinical-stage pharmaceutical company committed to helping people suffering from severe respiratory diseases to breathe better and live more fully. Using the power of nitric oxide, we’re bringing a powder-based drug to market to redefine the standard of care in a number of diseases and conditions, beginning with respiratory infections common in cystic fibrosis patients.
Q: Where did you get the inspiration from to pursue nitric oxide as an alternative to antibiotics for the treatment of CF patients?
A: During my 20-year tenure as a Professor of Chemistry at the University of North Carolina at Chapel Hill, my long-standing interest in nitric oxide as an antibacterial agent has been grounded in its critical role in many physiological processes in the human body, including our immune response to pathogens. As I continue to learn about the problems with antibiotics, including resistance, adverse side-effects, and lack of new antibiotics in drug pipelines, my interest in the need for alternative therapies for controlling bacteria has continued to flourish. A nitric oxide-release therapeutic mimics human physiology in eradicating bacteria in a broad action manner, making it a perfect alternative to ineffective antibiotics.
Q: Has the effect of nitric oxide been tested against healthy commensal bacteria as well as pathogenic bacteria? Furthermore, which bacterial species has the efficacy of nitric oxide treatment been tested against?
A: Our drug candidate is expected to act locally, therefore not influence commensal bacteria in the intestinal tract. Extensive microbiological work demonstrates that nitric oxide released from a macromolecular drug candidate is a never-before-seen therapeutic. As we focus on treating chronic infections in cystic fibrosis patients through the controlled and local delivery of inhaled macromolecules, we are initially targeting Pseudomonas aeruginosa – the bacteria most problematic to CF patients. We have tested the effect of nitric oxide against 29 different strains and have shown a 100% success rate in eradicating all superbugs tested so far, including the top 10 CF pathogens and over 12 superbugs defined by the World Health Organization and Center for Disease Control as severe threats to public health.
Q: Aside from reducing the ever-growing problem of antimicrobial resistance, does nitric oxide offer any other advantages in the treatment of chronic infection over more traditional broad-spectrum antibiotic treatments?
A: Nitric oxide plays a crucial role in physiological processes in the human body, including our immune system’s response to pathogens. As a natural antimicrobial that mimics the body’s response to pathogens, nitric oxide is an unprecedented alternative to antibiotics. Key advantages for using nitric oxide to treat chronic infections include:
- Its short half-life, which allows it to break down or oxidize much more easily than traditional antibiotics;
- Its small size and lack of charge, which enables rapid diffusion into mucus and biofilms to act on bacteria;
- Its ability to kill all bacteria due to its broad-spectrum activity;
- Its minimal side-effects on cells and tissue.
Vast Therapeutics recently announced results of a preclinical study investigating the efficacy of drug candidate, BIOC51.
Q: What is BIOC51?
A: BIOC51 is Vast Therapeutics’ first controlled NO-releasing powder-based drug candidate, which has eradicated every bacterial pathogen tested to date, making us the first company to achieve this level of in vitro eradication of multiple resistant bacteria. By using biopolymers as the inhaled delivery mechanism of BIOC51, we’re able to achieve highly affective targeting of NO to specific parts of the lungs via a nebulizer.
Q: Could you summarize the findings of the study?
A: Our recent study demonstrated the ability to significantly reduce the bacterial burden in a mouse model of Mycobacterium abscessus lung infection and our ability to eradicate all bacteria tested to date. M. abscessus causes chronic lung infections in cystic fibrosis patients and are difficult to overcome as they are multidrug-resistant. We were able to achieve a 99.9% reduction in M. abscessus counts in the lungs of mice treated once daily with BIOC51 for 8 days, without observable side effects—a truly unprecedented outcome given the difficulty of treating such infections.
Mark Schoenfisch, PhD, was speaking to Laura Elizabeth Mason and Karen Steward, PhD, Science Writers for Technology Networks.