Novel therapy for erosive bone disease

DESCRIPTION provided by applicant Osteoclasts OC are key mediators of erosive bone diseases including tumor associated osteolytic lesions as well as rheumatoid arthritis RA other forms of arthritis and osteoporosis Indeed OC are the only cells known to degrade bone Osteoclastogenesis begins with differentiation of monocytes into OC precursor cells OCP which subsequently differentiate into multinucleated OC with bone resorption activity Chiu Studies with antibodies Mensah and knock out in models Yagi demonstrate an absolute requirement for the Dendritic Cell Specific TrAnsMembrane Protein DC STAMP for the fusion of OCP to generate fully active OC Anti DC STAMP monoclonal antibodies attenuate the fusogenic process reducing the number of active OC Mensah thus providing a unique approach to erosive bone diseases Our Phase goal is to identify and characterize a human monoclonal anti DC STAMP antibody humAb as a therapy for erosive bone diseases We will construct a panel of humanized versions of DC STAMP specific mouse mAb A then express purify and characterize the candidate humAbs to be rank ordered using an in vitro assays of binding and osteoclastogenesis The functional activity of the top anti DC STAMP humAb will then be evaluated in a mouse model to explore application for multiple myeloma associated bone erosion Successful identification of a DC STAMP humAb will merit submission of a Phase application to fund IND enabling studies PUBLIC HEALTH RELEVANCE Skeletal metastases occur in multiple myeloma and other malignancies Current treatments are moderately effective yet fail to stop degradation of bone tissue and loss of joint function We have identified a monoclonal antibody that targets the master controller of bone loss in these diseases Besides its novel mechanism anti DC STAMP antibody therapy offers advantage safety due to highly specific nature of targeting and requirement for less frequent dosing With further development this antibody will greatly improve the therapeutic options for erosive bone diseases