AC-100, Novel Biological Approach to Promoting Dentin Formation in Humans

AC-100 (Dentonin®), 23-amino acid fragment of matrix extracellular phosphoglycoprotein (MEPE), acts specifically on committed odontoblast and osteoblast precursors to induce reparative dentin formation (in teeth) or bone regeneration (in bone defects). AC-100 does not induce ectopic bone or dentin. This mechanism of action is unique among the bone anabolic agents with similar potencies. Objectives: The objective of this clinical study was to evaluate the safety and efficacy of a unique approach to indirect pulp capping in humans – a peptide, AC-100, delivered through the dentin tubules. Methods: In a phase 2 double-blind repeat-dose study, 35 subjects, candidates for at least two 3rd molar extractions, were enrolled at Jean Brown Research (Utah). Subjects functioned as their own controls - one molar was treated with 200µg AC-100 (applied on days 0, 2, 4), the other with a placebo. Clinical parameters were used to assess patient comfort. On Day 60 the teeth were extracted, processed for routine histology and evaluated for reparative dentin formation, inflammation, necrosis and remaining dentin thickness (RDT). Results: AC-100 was well tolerated through this novel delivery route. No increase in inflammatory response, necrosis, or other complications were observed in AC-100 treated teeth in comparison to placebo treated teeth. No serious adverse events were reported. Importantly, post-hoc analyses demonstrated that AC-100 stimulates reparative dentin formation within a wide range of cavity depths. Best effects were observed where clinically most needed - in deep cavities with RDT<500µm, however positive effects were observed even at RDTs>2000µm. Conclusion: AC-100 appears to be safe and well tolerated novel biological approach to promote reparative dentin formation in humans when delivered through the dentin tubules. Notably, pre-clinical studies have demonstrated that AC-100 achieves its activity in a tissue protective physiologic manner, stimulating the existing pulp cells to produce dentin with reduced inflammatory and apoptotic responses.