An EP4 receptor agonist for enhancing alveolar bone regeneration in tooth-extract

DESCRIPTION (provided by applicant): Myometrics is in the early stages of developing a device consisting of a novel, non-protein osteogenic agent suspended in a collagen sponge that would be applied by the practitioner into the tooth socket following extraction for ultimate placement of dental implants. It is anticipated that this innovative device will increase the rate of bone regeneration sufficiently to significantly reduce the time for the production of high density bone needed for optimal implant osseointegration. Additionally because the active agent is a small molecule and not a protein, the anticipated cost of treatment is expected to be in the order of one-tenth that of existing therapies. This cost reduction will be a substantial differentiating factor for this agent and will have flow on effects to reduce the cost of implant procedures. We have chosen to advance this device in dental implant site preparation because of its potentially strong osteogenic activity. This is expected to result in both a shortening of the treatment time for dental implants as well as superior implant stability. We also anticipate that this agent will be able to be used in conjunction with the correction of bone loss associated with periodontal disease, alveolar ridge defects and in craniofacial reconstructive surgery. These additional applications all represent large clinical environments that are consistent with the NIDCR mission but for the sake of focus will not be looked at in this round. The osteogenic activity of this agent has been strongly suggested during an initial study in a rodent bone defect model. The main objectives covered by this grant application are to (1) positively establish the bone anabolic activity of this agent by quantitative analysis of the initial rodent bone defect study; (2) perform a time course study with purified MYM-101 in the calvarial defect model to assess the rate of new bone formation and identify a response time which gives an optimized experimental window; (3) perform a dose response study and quantitate the extent of newly formed bone using micro-CT analysis; and (4) complete the receptor pharmacology of purified MYM-101 using a transfected cell system and establish the in vitro efficacy of the agent using a bone marrow cell model of osteogenesis. The firm establishment of the osteogenic and receptor pharmacology properties of this agent will lead us to predict that this agent will be able to produce new bone in a tooth extraction model in dogs and subsequently in the jaws of human subjects. It is expected that the success of these feasibility studies will lead to a Phase II Proof of Principal study which, if successful, will generate sufficient interest among the dental pharmaceutical companies for Myometrics to be able to explore and establish a cooperative business relationship around the co-development of this agent. Additionally, if success is achieved in Phase I, studies will be initiated in the additional areas this agent is expected to work, such as the restoration of bone lost with advanced periodontal disease. PUBLIC HEALTH RELEVANCE: The continuing demand on dental implants therapy raises the need for further improvement of bone reconstruction techniques and materials. Providing adequate bone volume and quality is crucial for implant therapy. New therapies that increase the rate of bone formation exist but all of them are protein based and consequently very expensive which is a barrier to a more widespread use of dental implants. The small molecule device being developed by Myometrics is expected to equal or better the efficacy of existing therapies, have superior storage and handling characteristics and cost substantially less. As a consequence it is anticipated that it will extend this treatment option further into more challenging clinical cases.