Sulfated Carbohydrates for the Treatment of Periodontitis

Abstract Periodontitis affects over half of the American population and has no reliable form of treatment for any stage and grade of the disease besides antibiotics, tooth root scaling and planing and periodontal surgery with highly variable outcomes. This STTR application proposes to identify a structurally defined sulfated low molecular weight heparan sulfate as a novel therapeutic for treatment of periodontitis. Glycan Therapeutics LLC is a company specialized in synthesizing sulfated carbohydrates using innovative enzyme-based methods and produce large quantities of several carbohydrates currently being explored for biological use. One of the molecules, an 18-mer sulfated heparan sulfate, has been reported to be anti- inflammatory by our group and preliminary data shows a promising effect on promotion of bone homeostasis. This proposal is focused on the investigation of a specifically sulfated 18-mer length carbohydrate as a periodontal therapeutic in vitro and in vivo. Further, as the carbohydrate investigated proves to be both anti-inflammatory and bone anabolic in nature, it will be investigated in the context of high risk and more severe and hyperinflammatory forms of periodontitis such as in subjects with diabetes. The team consists of Dr. Patricia Miguez, clinician scientist, bone and extracellular matrix biologist and periodontist, and collaborators at UNC-CH and Dr. Vijay Pagadala, co-investigator from Glycan Therapeutics with significant experience in synthesis and characterization of such synthetic oligosaccharides. This proposal will provide valuable insights into the mechanism of action of such small sulfated carbohydrates in bone homeostasis, provide efficacy data in proof-of-concept studies in small animals and pave the way for a phase II proposal to evaluate such therapeutic for treatment of periodontitis in a large animal model and with development of an efficient and long-lasting intra-oral delivery system.