Psoriasis is a common immune-mediated disease that affects approximately 2% of the US and European populations and significantly impacts the quality of life. T cells are recognized as primary mediators of the disease and new generation therapies aimed at eliminating reactive T cells or interfering with the immunologic cascade caused by their activation have been shown to be effective in treating psoriasis. These biologic therapies have the advantage of selectively inhibiting T cell function and are expected to cause fewer systemic side effects than traditional interventions. However, currently available therapies may ultimately be limited by their high cost or if long-term patient follow-up studies yield unsatisfactory results. A current need exists to identify additional drug candidates that effectively inhibit T cell response yet possess limited systemic toxicity. The long-term goal of this research is to identify novel therapeutic agents that are effective in the treatment of psoriasis, safe for long-term use, and well tolerated. The immediate goal is to evaluate the actions of a new anthracycline analog, GPX-150, for use in the treatment of psoriasis. GPX-150 is a recently patented novel doxorubicin analog and preliminary data indicates it has dramatically reduced systemic toxicity compared to doxorubicin yet can effectively inhibit T cell function. Our central hypothesis is that GPX-150 will inhibit T cell activation, proliferation and alter cytokine production in a manner expected to disrupt the inflammatory cascade leading to the initiation and progression of psoriasis. The specific aims for the project are to: I) Determine whether GPX-150 inhibits T cell proliferation and activation. II) Determine whether GPX-150 inhibits the production of psoriasis related cytokines. Ill) Determine whether topical or systemic GPX-150 inhibits inflammation in a murine model of contact hypersensitivity and assess the achievable dermal concentrations of the drug. Proposed studies are expected to help determine the clinical and commercial potential of GPX-150 for treatment of psoriasis
