Sm STAMP Therapeutic
We have developed several lead STAMP molecules with specific and robust activity against Streptococcus mutans, a cavity-causing organism which adheres to the tooth surface and produces enamel-damaging acids after feeding on dietary sugars such as sucrose. These STAMPs can eliminate S. mutans from within multi-species biofilms (also known as dental plaque) without affecting closely related non-cariogenic oral bacteria (Figs. 1 and 2). Healthy, S. mutans-free biofilms can inhibit future S. mutans colonization subsequent acid production and cariogenesis. Current efforts are focused on preclinical activities such as formulation, oral availability, and safety.
Figure 2. Binding of STAMP Sm6(L1)B33 to S. mutans biofilms. Once bound by the STAMP, the S. mutans were effectively eliminated after a few minutes. The STAMP did not bind to biofilms grown from other oral bacteria. [Copyright © American Society for Microbiology, Antimicrobial Agents and Chemotherapy, May 2010, p. 2143-2151, Vol. 54, No. 5]
Figure 1. S. mutans, S. sanguinis, and S. gordonii planktonic cells were exposed to 25 µM of the STAMP C16G2 for 1 min. Surviving CFU per milliliter were detected and compared. Data represent averages of the results of at least three independent experiments [Copyright © American Society for Microbiology, Antimicrobial Agents and Chemotherapy, November 2006, p. 3651-3657, Vol. 50, No. 11]
Introduction to Product Candidate for Dental Caries Prevention
A novel product candidate, referred to as "C16G2", was designed as a specifically targeted antimicrobial peptide (STAMP) with specificity for Streptococcus mutans. The C16G2 peptide consists of two functional regions: an S. mutans-selective 'targeting region' comprised of a fragment of the S. mutans competence stimulating peptide (CSP); and a broad-spectrum antimicrobial peptide (G2). Our research has shown that C16G2 is bactericidal via a membrane disruption mechanism similar to other antimicrobial peptides. The very fast kinetics of C16G2's bactericidal activity against S. mutans confers its antimicrobial specificity (Kaplan, Sim et al. 2011) and provides for convenient administration by routes currently employed in dental practices. C16G2 is also bactericidal against early-stage and mature S. mutans biofilms and demonstrates selectivity for S. mutans in planktonic and biofilm-associated mixed culture systems (Eckert, He et al. 2006). Multi-species biofilms from which S. mutans has been eliminated by C16G2 resist re-colonization by S. mutans, thus demonstrating the distinguishing feature of this drug candidate: a protective colonization effect in vitro (Li, Guo et al. 2010). This product profile of C16G2 supports the rationale for it to be administered in a mouth rinse to selectively kill S. mutans while not affecting the other species in the oral biofilm.
One previous clinical trial of C16G2 has been reported in the literature (Sullivan et al. 2011). The objectives of the study were to assess the effects of a single application of C16G2 on S. mutans in saliva and dental plaque, on plaque pH, on lactic acid production after a sucrose challenge, and mineral loss from tooth enamel. The trial showed that a single application of 8 mg C16G2 to twelve human subjects resulted in the selective elimination of S. mutans from plaque and saliva while leaving the remaining flora relatively undisturbed. The treated group also had a higher resting plaque pH, lower lactic acid production, and a significant reduction in enamel mineralization (Sullivan et al. 2011).
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