The antimicrobial peptide M33 may be the long-sought substitute to treat difficult lung infections, like multi-drug resistant pneumonia.
In 2013, the European Respiratory Society predicted 3 millions cases of pneumonia in Europe every year. The standard treatment for pneumonia is an intravenous administration of a combination of drugs. This leads to the development of antibiotic resistance in the population. Gradually, doctors are running out of solutions to cure patients. An Italian company suggests a new option: the M33 peptide.
Few years ago, the Italian company SetLance SRL decided to investigate the M33 peptide. The antimicrobial peptide is an optimized version of an artificial peptide sequence selected for its efficacy and stability. So far, it showed encouraging in-vitro results against multidrug-resistant Gram-negative bacteria, including Klebsiella Pneumoniae. With the support of EU funding to the PneumoNP project, SetLance SRL had the opportunity to develop a new formulation of M33 that enhances its antimicrobial activity.
Fig. Action of a M33 peptide on the membrane of a gram-negative bacteria
The new formulation of M33 fights Gram-negative bacteria in three steps. First of all, the M33 binds with the lipopolysaccharides (LPS) on the outer membrane of bacteria. Then, the molecule forms a helix and finally disrupts the membrane provoking cytoplasm leaking. The peptide enabled up to 80% of mice to survive Pseudomonas Aeruginosa-based lung infections. Beyond these encouraging results, toxicity to the new M33 formulation seems to be much lower than antimicrobial peptides currently used in clinical practice like colistin.
Lately, SetLance scaled-up the synthesis route and is now able to produce several hundred milligrams per batch. The molecule is robust enough for industrial production. We may expect this drug to go on clinical development and validation at the beginning of 2018.
 Ceccherini et al., Antimicrobial activity of levofloxacin-M33 peptide conjugation or combination, Chem Med Comm. 2016;
Brunetti et al., In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate. Scientific Reports 2016
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