Immunoregulatory biomaterials for modulating arthritis flares

PROJECT SUMMARY Uncontrolled disease fluctuations in a subset of joints, referred to as flares, can be a common experience in autoimmune arthropathies even in the context of overall good disease control with disease-modifying anti- rheumatic drugs (DMARDs). Standard-of-care non-steroidal anti-inflammatory drugs and/or corticosteroids can

provide temporary symptomatic relief, but these are ineffective at preventing recurrence and flare-mediated joint damage. An unmet need exists for durable flare control agents that potentially complement standard-of-care DMARDs. The objective of the fellowship application is to develop and test a nanoparticle-based

immunomodulatory agent for enhancing local flare control while avoiding generalized immunosuppression. The agent is delivered to the lymph nodes proximal to the inflamed joint where pre-existing antigen presenting cells, widely recognized as key activators of autoreactive cells, are harnessed to promote flare protection. Aim 1 will

optimize the agent and measure local and systemic concentrations to identify the safe dose range for achieving modulation of antigen presenting cells and durable flare control. Aim 2 will identify potential biomarkers for agent responsiveness and assess flare control in combination with a standard-of-care DMARD. The results of this

project will assess feasibility of promoting immunomodulatory antigen presenting cells to improve flare control in a well-established mouse model of autoimmune arthritis. If successful, in the longer term, the project will pave the way for a new approach to treat flares and advance the NIAMS mission of developing new

treatments for unmet needs in arthritis. The training program will enrich the applicant's knowledge and skills in immunoengineering, drug delivery and autoimmune disease. Gaining expertise and scientific competency in the subject matter through the project will prepare the applicant for a career in rheumatic disease research.