Replacement Therapy
Background. Our licensed, patented replacement therapy technology is the fruit of 25 years of research. This technology, which is licensed from the University of Florida, provides us with an exclusive world wide license. Most human tooth decay is caused by a bacterium called Streptococcus mutans that sits on the tooth surface and converts sugar in our diet to lactic acid. The lactic acid is excreted by the bacteria and causes tooth decay by dissolving the mineral that comprises our enamel and dentin. Our scientists have isolated a strain of S. mutans that produces a small amount of an antibiotic that is capable of killing all other strains of this species. Through recombinant DNA technology, we succeeded in eliminating the gene in this strain that is responsible for producing lactic acid. Consequently, it does not cause significant tooth decay. This genetically modified strain will be used in an approach called replacement therapy to eliminate decay-causing strains of S. mutans, with the possibility of providing life-long protection from a single, five minute treatment.
Technical Background. Many different types of bacteria reside in everyone's mouth. Streptococcus mutans (S. mutans) is a bacterium that resides on nearly everyone's teeth. This bacteria converts sugar that we eat into lactic acid. Lactic acid erodes the tooth's enamel and causes the great majority of tooth decay. Our replacement therapy technology consists of a genetically modified strain of S. mutans that does not produce lactic acid. Our strain of S. mutans produces tiny quantities of a substance known as Mutacin 1140, which allows our strain to out-compete any strain of S. mutans that is naturally resident on a person's teeth. Our strain eliminates the resident strain of S. mutans and replaces it in the mouth. The manufacturing methods for producing our strain of S. mutans to be used in our replacement therapy technology will be standard fermentation methods. It will be administered as a pharmaceutical composition by dentists during office visits. Administration will consist simply of swabbing our strain onto the patient's teeth using a cotton tipped applicator for a five minute period. Because our strain out-competes resident strains on teeth, one treatment may last for a lifetime.
Pre-Clinical Studies. Laboratory and animal studies of the effectiveness of our replacement therapy technology have been conducted in rats for almost 30 years. In one of these studies, our strain of S. mutans and wild-type strains of S. mutans were grown in the laboratory in the presence of sugar. After careful analysis of the culture, it was found that the wild-type strain made lactic acid almost exclusively from the metabolism of sugar, as well as very small amounts of other acids and non-acidic compounds. By contrast, our strain made mostly the non-acidic compounds and produced absolutely no detectable lactic acid. We then infected 2 identical groups of conventional rats with either the wild strain or our strain. A third identical group of rats was not infected and served as a control group. After feeding the rats a diet containing sugar for 8 weeks, the teeth of the rats were carefully inspected to determine their incidence and severity of tooth decay. It was found that animals infected with our strain had no more tooth decay than did the control group animals. Both the group infected with our strain and the control group had only a fraction of the tooth decay experienced by the wild-type strain.
We have demonstrated that our strain can eliminate disease-causing S. mutans strains in laboratory animals. However, the treatment did not affect the levels of other types of bacteria commonly found in the oral cavity. No acute or chronic side-effects were observed in treated rats. The strain was also shown to be very stable genetically.
Regulatory Status. Our investigational new drug (IND) application was approved by the US Food and Drug Administration (FDA) on November 30, 2004. We expect to initiate the Phase I clinical trial to establish safety in the first half of 2005.
General-interest Articles (Click links below to view articles where available)
USA Today: Gen-Mod Dental Treatment Gets Approval For Human Testing
Oragenics has won approval to conduct human trials of a dental treatment that uses genetically modified bacteria to prevent cavities for a lifetime... December 2004
The New York Times: Bacteria Enlisted for New Trials on Dental Health [ PDF - 131kb ]
Can genetically engineered bacteria prevent tooth decay? Oragenics is about to take the first step toward answering that question... November 2004.
Explore Magazine: Tackling Tooth Decay [ PDF - 2.7mb ]
Tooth decay, it's the most common childhood disease. Oragenics hopes to prevent a lifetime of tooth decay... Office of Research Pubications, University of Florida, August 2004.
Popular Science: Can Genetically Engineered Bacteria Cure Tooth Decay?
Kids get cavities. Dentists fill them. It's a fairly old arrangement, but it may soon come to an end... July 2004
THE WALLSTREET JOURNAL: Look, Ma, No Cavities! Oragenics is Offering an Oral Rinse for Life [ PDF - 92kb ]
A lifetime without cavities after a painless, five minute visit to the dentist probably sounds too good to be true. But Oragenics... October 29, 2003.
Fortune.com: Germs Make the Man [ PDF - 65kb ]
Your body is teeming with trillions of infectious microbes. That's a very good thing... February 2003.
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Scientific Articles (Click links below to view articles where available)
Hillman, J.D., Mo, J., McDonell, E., Cvitkovitch, D., and Hillman, C.H. Modification of an effector strain for replacement therapy of dental caries to enable clinical safety trials. Journal of Applied Microbiology 2007:102:1209-1219.
View Abstract
“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”, (M.A. Riley and O. Gillor ed.), Research and Applications in Bacteriocins 2007.
Hillman, J.D. 2002. Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie van Leeuwenhoek 82:361-366.
Hillman, J.D. 2001. Replacement therapy of dental caries. Oper. Dent. Suppl. 6:43-53.
Hillman, J.D., Brooks T.A., Michalek S.M., Harmon C.C., Snoep J.L., and Van Der Weijden C.C. "Construction and Characterization of an Effector Strain of Streptococcus mutans for Replacement Therapy of Dental Caries. Infection and Immunity, 2000;68(2):543-549. http://iai.asm.org
Hillman, J.D. 1999. Replacement therapy of Dental Caries. In: Dental Plaque Revisited: Oral Biofilms in Health and Disease. (H.N. Newman and M. Wilson, eds.) Bioline, Cardiff, UK., pp. 587-599.
Hillman J.D. "Principles of Microbial Ecology and Their Application to Xerostomia-Associated Opportunistic Infections of the Oral Cavity." Adv. Dent. Res. 1996;10(1):66-68. http://adr.iadrjournals.org
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