Mutacin 1140™ ("MU1140")
Background. Mutacin 1140™ ("MU1140") is a licensed, patented technology that is an antibiotic peptide which is produced by our strain of S. mutans. It was discovered in the course of the research into our SMaRT Replacement Therapy™ technology. It is a broad-spectrum antibiotic that has demonstrated potency in laboratory studies against essentially all Gram-positive bacteria against which it has been tested. Our Mutacin 1140™ ("MU1140") technology, which is held under license from the University of Florida, provides us with an exclusive world wide license.
Before the development of effective modern antibiotics, serious bacterial infections were as feared as AIDS is today. Since development of antibiotics, they have been less feared. However, society may soon be faced once again with the prospect of bacterial and fungal diseases becoming major causes of death. Resistance of medically important microorganisms to frontline and last-line of defense antibiotics is increasing at a faster pace than development of drugs which are effective against them.
Technical Background. In vitro laboratory studies conducted by us have demonstrated Mutacin 1140™'s ("MU1140") effectiveness against essentially all tested Gram-positive bacteria and certain medically important Gram-negative bacteria as well. Bacteria, including those responsible for "strep throat", common pneumonia, gastric ulcers, and listeriosis, are killed by Mutacin 1140™ ("MU1140") . Mutacin 1140™ ("MU1140") belongs to a small class of antibiotics called lantibiotics. Lantibiotics differ from other antibiotics because they contain an unusual amino acid. They are able to kill a wide variety of bacteria by binding to a cell wall component, Lipid II, a molecule that is essential for bacterial cell growth.
Preclinical Studies. By mid-2005 we made significant breakthroughs in the production and purification of Mutacin 1140™ ("MU1140") and initiated pre-clinical studies. We have concluded two preclinical studies with Mutacin 1140™ ("MU1140"), utilizing independent testing labs, that provided positive results on Tier 2 spectrum of activity against clinically important Gram-positive bacteria (including Staph aureus, Enterococcus faecalis, and Clostridium difficile) and the effectiveness of Mutacin 1140™ ("MU1140") when administered by intravenous injection to mice infected intraperitoneally with a lethal dose of Staphylococcus aureus.
A particularly interesting feature of Mutacin 1140™ ("MU1140") is that none of the sensitive species of bacteria tested were able to acquire genetically stable resistance to purified Mutacin 1140™ ("MU1140"). Acquired resistance to antimicrobial agents by strains of bacteria that cause illness in humans has become a major problem in the recent past.
Regulatory Status. We expect to complete additional animal safety trials, file an Investigational New Drug application ("IND") with the FDA in the first half of 2008 and once FDA approval is received, we plan to begin a Phase I clinical study.
General-interest Articles (Click links below to view articles)
Better Homes and Gardens - Antibiotic Resistance
March, 2001 article discusses how germs can mutate and survive new antibiotics and medicines.
Antimicrobial Resistance Response to a Growing Problem
This statement from the National Institutes of Health discusses the emerging problem of antibiotic resistance.
Scientific Articles (Click links below to view articles if available)
Hasper, H.E., Kramer, N.E., Smith, J.L., Hillman, J.D., Zachariah, C., Kuipers, O.P., de Kruijff, B. and Breukink, E. Cell wall precursor abduction as a novel antibiotic mechanism. Science, Submitted.
Smith, J.L., Orugunty, R., and Hillman, J.D. Lantibiotic Production by Streptococcus mutans: Their Uses in Replacement Therapy for the Prevention of Dental Caries and as Antibiotics for the Treatment of Various Infectious Diseases. Horizon Scientific Press, Rowan House, 28 Queens Road, Hethersett, Norwich, NR9 3DB, UK, in press.
Smith, L., Zachariah, C., Thirumoorthy, R., Rocca, J., Novák, J., Hillman, J.D. and Edison, A.S. 2003. Structure and dynamics of the lantibiotic mutacin 1140. Biochem. 42:10372-10384.
Smith L., Novák, J., Rocca J., McClung S., Hillman J.D. and Edison A.S. "Covalent Structure of Mutacin 1140 and a Novel Method for the Rapid Identification of Lantibiotics." Eur. J. Biochem. 2000;267:6810-6816.
Hillman J.D., Novák, J., Sagura E., Gutierrez J.A., Brooks T.A., Crowley P.J., Hess M., Azizi A., Leung K.P. Cvitkovitch D., and Bleiweis A.S.. "Genetic and Biochemical Analysis of Mutacin 1140, a Lantibiotic from Streptococcus mutans." Infection and Immunity 1998;66(6):2743-2749.
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