Articulate Biosciences, LLC — Department of Health and Human Services SBIR Phase I: NIA

Description

ABSTRACT Many disease processes cause bodily tissues to experience high friction and concomitant pain including dry eye vaginal dryness and osteoarthritis Thus there is an unmet clinical need for new biomaterial based lubricants Of these diseases osteoarthritis OA is a complex disease that afflicts approximately million Americans and of all people years OA occurs due to progressive break down of articular cartilage the tissue that distributes loads applied to articulating joints Specifically associated with OA is a deterioration of the lubricating properties of the synovial fluid this deterioration arises from the synovial fluid s naturally occurring hyaluronic acid HA becoming lower molecular weight and a loss of the glycoprotein lubricin This renders the cartilage prone to further wear along with increased patient pain and reduced mobility until a total knee replacement surgery is required Viscosupplementation the intra articular injection of HA is one treatment which has a US market of $ billion $ billion globally However HA exhibits a short residence time in the joint as it is rapidly degraded and cleared and there are conflicting reports of HA s efficacy in protecting the articular cartilage Consequently the leading US orthopedic society no longer recommends its use To address this unmet patient need we have developed a non HA injectable medical device lubricant that is a bio inspired synthetic polymer rather than HA and therefore is not susceptible to rapid enzymatic degradation is crosslinked into a large macromolecular network to significantly slow diffusion out of the joint and dramatically lengthen residence time and demonstrates reduction in friction and wear i e protection of ex vivo cartilage whereas existing viscosupplement products have not been shown to protect cartilage Our preliminary data demonstrating protection of cartilage and long residence time along with the proposed class of polymer s history of use in FDA approved devices support the promising potential of this bioinspired synthetic material as a novel lubricant The aims of this proposal are Specific Aim Determine the mechanism of lubrication of novel lubricants Specific Aim Develop product specifications and scale up pMPC synthesis g to g scale Specific Aim Evaluate lubricant cyto and whole organ tissue compatibility with six relevant cell lines and with clearance organs of rats previously injected intraarticularly with lubricant Development Plan Successful completion of Aims will de risk and add value to this patent pending technology enabling further development Phase II SBIR to assess large animal efficacy and biocompatibility ISO and pharmacokinetics studies to apply for an Investigational Device Exemption This technology will be highly attractive to major orthopedic companies as a thoroughly developed OA injectables market physician training marketability reimbursement already exists making this product readily adoptable PROJECT NARRATIVE This proposal aims to establish the feasibility of synthetic biologically inspired polymers as lubricants for diseased tissues suffering from painful high friction As a first therapeutic area these innovative injectable lubricants will be of interest to the approximately million individuals in the U S with osteoarthritis as they will protect joints from wear and will last for a greater duration in the joint than the currently available injectable treatments This material and mechanistic based proposal will investigate the lubricant s mechanism of action synthetic scalability and biocompatibility to provide the scientific merit and basis for developing this type of therapeutic medical device Class III