Ceragenins, also known as CSAs, are synthetic, non-peptide small molecule mimetics of endogenous host defense or antimicrobial peptides. Ceragenins have broad-spectrum activity mimicking those of endogenous host defense peptides. However, ceragenins, are not peptides. They are synthetic small molecules that can be manufactured in large scale and are not subject to proteolytic degradation. N8 Medical is developing several ceragenin coating products tat can be deployed as a platform across the medical device market and that provide the flexibility and customization needed to address infection prevention in each medical device category.
Ceragenins demonstrate antimicrobial, anti-inflammatory, and anti-cancer activity. The antimicrobial activity extends to Gram negative and Gram positive bacteria, including multi-drug resistant strains and carbapenem resistant strains, biofilms, and fungi. Over 100 ceragenins have been synthesized to date. Ceragenins are synthetically produced small molecule chemical compounds consisting of a sterol backbone with amino acids and other chemical groups attached to them. These compounds have a net positive charge that is electrostatically attracted to the negatively charged cell membranes of certain viruses, fungi and bacteria. Ceragenins have a high binding affinity for such membranes and are able to rapidly disrupt the target membranes leading to rapid cell death. While ceragenins have a mechanism of action that is also seen in antimicrobial peptides, which form part of the body’s innate immune system, they avoid many of the difficulties associated with the use of antimicrobial peptides as medicines.
Lead ceragenin compounds, has exhibited potent antimicrobial properties and are rapidly bactericidal, fungicidal and virucidal against a wide array of pathogens, including multidrug resistant strains of Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pseudomonas). These ceragenins have also demonstrated the ability to both prevent and eradicate bacterial and fungal biofilms, which are nearly impossible to eradicate utilizing conventional antibiotics. Preclinical testing has displayed high potency at low doses, and the absence of toxic response at doses much higher than those that are expected to be clinically necessary.
Ceragenins have been the subject of more than over 45 peer-reviewed articles, numerous patents, and several NIH funding awards.
Direct links to select peer-reviewed journal articles regarding ceragenins can be found below:
- Candidacidal Activity of Selected Ceragenins and Human Cathelicidin LL-37 in Experimental Settings Mimicking Infection Sites. Bonita Durnaś, Urszula Wnorowska, Katarzyna Pogoda, Piotr Deptuła, Marzena Wątek, Ewelina Piktel, Stanisław Głuszek, Xiaobo Gu, Paul B. Savage, Katarzyna Niemirowicz, Robert Bucki (2016).
- Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection. Robert Bucki, Katarzyna Niemirowicz, Urszula Wnorowska, Fitzroy J. Byfield, Ewelina Piktel, Marzena Watek, Paul A. Janmey, Paul B. Savage (2015).
- CSA-131, a ceragenin active against colistin-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates. Xavier Vila-Farrés, Anna Elena Callarisa, Xiaobo Gu, Paul B. Savage, Ernest Giralt, Jordi Vila (2015).
- Bactericidal Activities of Cathelicidin LL-37 and Select Cationic Lipids against the Hypervirulent Pseudomonas aeruginosa Strain LESB58. Urszula Wnorowska, Katarzyna Niemirowicz, Melissa Myint, Scott L. Diamond, Marta Wróblewska, Paul B. Savage, Paul A. Janmey, Robert Bucki (2015).
- Local Delivery of the Cationic Steroid Antibiotic CSA-90 Enables Osseous Union in a Rat Open Fracture Model of Staphylococcus aureus Infection. Aaron Schindeler, PhD, Nicole Y.C. Yu, PhD, Tegan L. Cheng, BE/BMedSci, Kate Sullivan, PhD, Kathy Mikulec, Lauren Peacock, Ross Matthews, BVSc, Dip Vet Clin Path, and David G. Little, FRACS(Orth), PhD (2015).
- In Vitro Bactericidal and Bacteriolytic Activity of Ceragenin CSA-13 against Planktonic Cultures and Biofilms of Streptococcus pneumoniae and Other Pathogenic Streptococci. Miriam Moscoso, María Esteban-Torres, Margarita Menéndez, Ernesto García (2014).
- Optimization of Ceragenins for Prevention of Bacterial Colonization of Hydrogel Contact Lenses. Xiaobo Gu, Jacob D. Jennings, Jason Snarr, Vinod Chaudhary, Jacob E. Pollard, and Paul B. Savage (2013).
- Study of the effect of antimicrobial peptide mimic, CSA-13, on an established biofilm formed by Pseudomonas aeruginosa. Carole Nagant, Betsey Pitts, Philip S. Stewart, Yanshu Feng, Paul B. Savage & Jean-Paul Dehaye (2013).
- In vivo efficacy of a silicone‒cationic steroid antimicrobial coating to prevent implant-related infection. Dustin L. Williams, Bryan S. Haymond, James P. Beck, Paul B. Savage, Vinod Chaudhary, Richard T. Epperson, Brooke Kawaguchi, Roy D. Bloebaum (2012).
- Effect of a low concentration of a cationic steroid antibiotic (CSA-13) on the formation of a biofilm by Pseudomonas aeruginosa. C. Nagant, Y. Feng, B. Lucas, K. Braeckmans, P. Savage, J.P. Dehaye (2011).
- Ceragenins: A Class of Antiviral Compounds to Treat Orthopox Infections. Michael D. Howell, Joanne E. Streib, Byung Eui Kim, Leighann J. Lesley, Annegret P. Dunlap, Dianliang Geng, Yanshu Feng, Paul B. Savage and Donald Y.M. Leung (2009).
- Antimicrobial Activities of Ceragenins against Clinical Isolates of Resistant Staphylococcus aureus. Judy N. Chin, Michael J. Rybak, Chrissy M. Cheung, and Paul B. Savage (2007).
Direct links to select articles relevant to the ceragenin technology and N8 Medical’s products under development can be found below:
- AMR: a major European and Global challenge. European Commission (2016).
- The interconnection between biofilm formation and horizontal gene transfer. Jonas Stenløkke Madsen, Mette Burmølle, Lars Hestbjerg Hansen, Søren Johannes Sørensen (2012).
- Electron microscopic analysis of biofilm on endotracheal tubes removed from intubated neonates. Karen B. Zur, MD, David L. Mandell, MD, Ronald E. Gordon, PHD, Ian Holzman, MD, and Michael A. Rothschild, MD (2004).
- Biofilms and device-associated infections. Rodney M. Donlan (2001).