ABSTRACT
Sjögren's disease is an autoimmune condition characterized by chronic inflammation and diminished secretory
function of the salivary glands. Although extensive investigation has been done to understand it, causes of and
effective treatments for the disease are still unknown. Given the high degree of need and the limitations of current
therapies, development of novel treatments to decrease inflammation and restore salivary gland secretory
function is essential. Previous studies demonstrated that a treatment with aspirin-triggered RvD1 and
dexamethasone (AT-RvD1/DEX) reverses Sjögren's disease-like features in NOD/ShiLtJ mice at disease onset
but the utility of this treatment is currently limited because the minimum effective dosage has yet to be
established. Specifically, although AT-RvD1 has no known side effects, its relatively high cost could limit
affordability. More importantly, DEX has been demonstrated to have significant side effects that can be expected
to impede long-term use. By determining AT-RvD1/DEX biodistribution using mathematical modeling and thus
defining the optimal (i.e., minimum effective) treatment dose, it is possible to manage the issues presented by
both drugs and in so doing produce a cost-effective and clinically safe treatment option to mitigate symptoms
associated with Sjögren's disease. To that end, it is hypothesized that systemic delivery of AT-RvD1/DEX will
restore salivary gland secretory function in Sjögren's disease. Aim 1 will reduce AT-RvD1/DEX doses to their
minimum effective levels, while Aim 2 will explore mechanisms by which AT-RvD1/DEX treatment outcomes are
achieved and Aim 3 will apply AT-RvD1/DEX treatment to humanized systems.
