Two non-toxic short peptides were conjugated to form a novel drug candidate. One of the peptides is a polymyxin-B or polymyxin-E analog (PMBN or PMEN, respectively) while the other is an immune cell chemotactic peptide (fMLF). The resultant new drug candidates (PMBN-fMLF or PMEN-fMLF) exhibit three antimicrobial activities: (a) it binds specifically to gram negative bacteria, thus enhancing penetration of antibiotics into the bacteria and (b) it promotes bacterial killing by blood phagocytes and (c) It binds to free LPS in the blood thus reduces effect on patients.
Project ID : 10-2007-98
Technology
Two non-toxic short peptides were conjugated to form a novel drug candidate. One of the peptides is a polymyxin-B or polymyxin-E analog (PMBN or PMEN, respectively) while the other is an immune cell chemotactic peptide (fMLF). The resultant new drug candidates (PMBN-fMLF or PMEN-fMLF) exhibit three antimicrobial activities: (a) it binds specifically to gram negative bacteria, thus enhancing penetration of antibiotics into the bacteria and (b) it promotes bacterial killing by blood phagocytes and (c) It binds to free LPS in the blood thus reduces effect on patients.
The Need
Bacteremic infections (when bacteria enter the blood stream), caused by bacteria and by Gram-negative bacilli in particular, constitute one of the major infectious disease problems in modern medicine. Antibiotic treatment is often administered too late, usually when symptoms appear, and before bacterial sensitivity to antibiotics is determined. The mortality rate due to bacterial septicemia is thus very high.
Advantages
Rapid and effective destruction of bacteria via dual complementary killing mechanisms.
Development of resistance is not anticipated owing to it's novel mode of action.
Applications
Co –administration with antibiotics in the Treatment of septicemia and bacteremia and possibly in the treatment of other Gram Negative infections.
Stage of Development
PMBN-fMLF was found to be active on a large number of clinical isolates. In vivo experiments in mice showed protection against Klebsiella pneumoniae following treatment with the drug. LD50 value of PMBN-fMLF is ~3 fold lower than polymyxin-B.
PMEN-fMLF exhibited potent in vitro and in-vivo anti-bacterial activity with a ~10 fold decrease in LD50, when compared to polymyxin-E.
Patent status
Granted US (7,435,716) & EU (EP 1 351 992) (DE, FR, UK)
Project manager
Elisha Natan
Director BD
Project researchers
Itzhak Ofek
T.A.U Tel Aviv University, Medicine-Sackler Faculty
Clinical Microbiology and Immunology
Matityahu Fridkin
Weizmann Institute of Science (WIS),
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