Project Grant R42DE028212

A NOVEL REMEDY FOR PERIODONTAL BONE LOSS - PERIODONTITIS IS A COMMON CHRONIC INFLAMMATORY DISEASE CHARACTERIZED BY DESTRUCTION OF THE SUPPORTING STRUCTURES OF THE TEETH (THE PERIODONTAL LIGAMENT AND ALVEOLAR BONE). THE TOTAL PREVALENCE OF PERIODONTITIS IN ADULTS AGED 30 YEARS AND OLDER WAS 47.2% (REPRESENTING ABOUT 64.7 MILLION ADULTS AGED 30 YEARS AND OLDER) AND 70.1% IN ADULTS AGED 65 YEARS AND OLDER IN THE U.S. THE CURRENT TREATMENT OPTION FOR PERIODONTAL DISEASES INVOLVES MECHANICAL DEBRIDEMENT - SCALING AND ROOT PLANING WHICH REQUIRES FREQUENT AND MULTIPLE VISITS TO THE DENTIST AND IS SOMETIMES FOLLOWED BY ADJUNCTIVE THERAPY OF LOCAL DELIVERY OF ANTIMICROBIALS OR SYSTEMIC ANTIBIOTICS SUCH AS DOXYCYCLINE. THE DISADVANTAGES OF CURRENT TREATMENT OPTIONS ARE INCONVENIENT AND PAINFUL EXPERIENCE, FAILURE OF ANTIMICROBIAL TO PENETRATE BEYOND BIOFILM SURFACE LAYER, RISKS TO PROMOTE ANTIMICROBIAL RESISTANCE, AND SYSTEMIC SIDE EFFECTS. OTHER LIMITATION OF CURRENT TREATMENT IS THAT NONE OF THESE DRUGS ARE TARGETING HOST AND PERIODONTAL BONE LOSS. THERE IS A MAJOR VOID IN PERIODONTAL DISEASE THERAPEUTICS PRODUCTS WHICH CAN TARGET HOST RESPONSE AND IS EASY TO USE. THE GLOBAL PERIODONTAL DISEASE THERAPEUTICS MARKET IS ANTICIPATED TO GAIN A GROWTH OF 8.7% FROM 2016 TO 2024. AT THIS PACE, THE MARKET IS ESTIMATED TO REACH A VALUATION OF US$537.2M BY THE END OF THE FORECAST PERIOD. PERIOMICS CARE IS AN EARLY-STAGE NEW YORK BASED BIOTECHNOLOGY COMPANY THAT WAS ESTABLISHED TO COMMERCIALIZE A NOVEL ORAL GEL FORMULATION FOR TREATMENT OF PERIODONTAL DISEASE. IN PHASE I WE HAVE SYNTHESIZED, FORMULATED, TESTED AND PATENTED POC7A, AN ANTAGONIST FORMULATION TO TARGET SUCCINATE RECEPTOR (SUCNR1) AS A TREATMENT FOR PERIODONTAL DISEASE. IN PHASE II PERIOMICS CARE PROPOSES TO SCALE UP THE SYNTHESIS AND FORMULATION OF POC7A TO CONDUCT PHARMACOKINETICS/ PHARMACODYNAMICS, AND TOXICITY OF POC7A IN BEAGLE DOGS (AIM1). WE WILL FURTHER TEST THIS FORMULATION IN LIGATURE INDUCED NON-HUMAN PRIMATE (NHP) MODEL TO VALIDATE OUR FINDING THAT POC7A EFFECTIVELY RESCUES PERIODONTAL BONE LOSS (AIM 2). NHP MODEL IS THE BEST SUITABLE MODEL FOR THIS STUDY BECAUSE THEY HAVE A HIGH DEGREE OF RESEMBLANCE IN TERMS OF PATHWAYS OF PHYSIOLOGICAL RESPONSES AND TARGETS THAT ARE RELEVANT TO HUMAN DISEASE. MORE IMPORTANTLY NHP HAVE ORAL STRUCTURES AND TEETH SIMILAR TO THOSE OF HUMANS AND HAVE NATURALLY OCCURRING DENTAL PLAQUE, CALCULUS, ORAL MICROBIAL PATHOGENS AND DEVELOP SIMILAR PERIODONTAL SYMPTOMS. THE PREMISE OF THIS PROPOSAL IS BASED ON OUR FINDINGS IN PHASE I THAT BLOCKING SUCNR1 BY POC7A CAN REDUCE INFLAMMATION, ALTER SUBGINGIVAL MICROBIOME AND RESCUE BONE LOSS. THE TECHNOLOGY AND FORMULATION DEVELOPED IN PHASE I IS NOW IP PROTECTED. THE FUNDS GAINED FROM THIS STTR PHASE II GRANT WILL BE USED FOR (1) SYNTHESIS AND TESTING OF THE FORMULATION, AND (2) DETERMINING THE EFFICACY OF THE FORMULATION IN PERIODONTAL NHP MODEL. THE OUTCOMES FROM THIS STUDY WILL HELP THE COMPANY TO SEEK FDA APPROVAL FOR THE OPTIMAL FORMULATION AND CONDUCT CLINICAL TRIALS FOR THE TREATMENT AND PREVENTION OF PERIODONTAL DISEASE.