Anti-inflammatory bioconjugates for sustained inhibition of post-traumatic osteoarthritis following joint injury

Project Summary Inan estimatedmillion Americans experienced symptoms of osteoarthritisOAthat could be associated with a known joint injuryDue to a lack of disease modifying therapiesjoint replacement surgery is often the only treatment option to eliminate the associated discomfort and restore mobility for patients with post traumatic osteoarthritisPTOAAnti inflammatory therapy has been proposed to inhibit key factors that have a well known role in mediating joint inflammation and subsequent tissue damage in PTOAHoweverdue to significant risks that are associated with exposing the patient to anti inflammatory drugs outside of the target tissueit is preferable to inject them directly into the affected jointUnfortunatelycurrently available drugs for this purpose are rapidly cleared from the joint spaceand they need to be re administered at least weekly to maintain a therapeutic effectThusthis potentially disease modifying treatment strategy for PTOA is limited b y the high frequency of drug dosing that would be requiredTo enable longer acting drug activity within a specific tissuewe have developed a platform biotechnology for generating clusters of anti inflammatory drugs to improve their clinical performanceWe can control the number of drug repeats in each cluster to engineer their potency and duration of bioactivityIn our preliminary studiesdrugs that have been modified using our technology exhibited superior treatment effects to inhibit inflammation compared to equivalent doses of an unmodified version of each drugWe believe a new drug based on our technology will remain within the joint for at leastweeks after administrationThereforeour strategy is well suited to provide long term inhibition of inflammation in a joint after injury and prevent further inflammation mediated joint damageIn this projectwe will show how increasing the size of our drug clusters will generate sustained treatment effects in the joint space to inhibit injury induced inflammation and prevent further damage from accumulating in the jointAs a part of this projectwe will measure the amount of time that our drug remains in the joint compared to currently available productsWe will also verify that a longer residence time in the joint will be sufficient to prevent the development of PTOA using a preclinical modelThis project will demonstrate proof of concept for our technology to provide sustained anti inflammatory therapy in a joint after injury Relevance Inan estimatedmillion Americans experienced symptoms of osteoarthritisOAfollowing joint injurywhich is a condition known as post traumatic osteoarthritisPTOAValitor has developed a novel drug that is designed for sustained inhibition of the mechanisms that lead to trauma induced arthritisOur proposed study will provide an initial proof of concept for our drugwhich could be used to prevent chronic pain and long term joint degeneration