Ceragenix Pharmaceuticals, Inc., a biopharmaceutical company focused on infectious disease and dermatology, has entered into a research and development agreement with an internationally recognized research laboratory to develop formulations, in the form of nasal ointments, designed to prevent influenza infection and to decolonize the nasal passage of methicillin-resistant staph aureus (MRSA).
The nasal ointments will contain the company's CSA-13, a member of the class of proprietary Ceragenin compounds, which has been shown in in vitro testing to prevent influenza infection of epithelial cells and to be highly bactericidal against MRSA. Pending successful formulation, the company plans on proceeding with further drug development activities.
MRSA is a form of staphylococcus that is now resistant to many antibiotics and represents nearly 70 percent of all staph infections found in hospital settings. Nasal ointments containing mupirocin are now commonly used to decolonize patients who carry MRSA in their nasal fluid, however there have been recent reports of increasing resistance to mupirocin. Studies suggest that prolonged and widespread use of mupirocin is associated with the development of resistance.
CSA-13 has undergone a broad range of in vitro testing and has shown excellent bactericidal activity against both gram-positive and gram-negative bacteria including all strains tested of MRSA (both hospital and community-associated) and vancomycin resistant strains (VISA and VRSA). Unlike Ceragenins, most antibiotics do not kill the bacteria but rather inhibit their growth. CSA-13 is a small, non-peptide molecule that mimics the activity of naturally occurring anti-infective compounds found in the human body (cathelicidin and defensins), which form part of the human innate immune system.
CSA-13 has also undergone in vitro testing at a major university in the United States where it showed the ability to prevent influenza infection by H3N2, one of the common strains of Type A influenza. While different strains of influenza have different protein structures, they all share in common the same negatively charged phospholipids in their viral membranes. CSAs have a net positive charge that is electrostatically attracted to the negatively charged cell membranes of certain viruses, including influenza, as well as fungi and bacteria.
"We believe that because the compound attacks the viral membrane, rather than the protein structures, which vary from strain to strain, CSA-13 may prove to be effective in preventing infection against all strains of influenza, regardless of genetic mutations," stated Steven Porter, Chairman and CEO of Ceragenix. "Testing is underway to see whether the compound is also effective against the avian flu strain H5N1. Our goal is to develop products that may be effective in reducing both the morbidity and mortality associated with MRSA infections, and reducing the risk of influenza."
Nasal exposure creates a route for influenza infection. According to the World Health Organization's Writing Group, most influenza outbreaks among humans suggest that virus-laden large droplets, generated when infected persons cough or sneeze, are the predominant mechanism of influenza virus transmission and that inhalation of these large droplets is believed to be the major mode of transmission.
Ceragenins, or CSAs, are synthetically produced small molecule chemical compounds comprised 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. CSAs have a high binding affinity for such membranes (including Lipid A) and are able to rapidly disrupt the target membranes leading to rapid cell death. While CSAs 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 their use as medicines.