Folate receptor-targeted therapies for inflammatory and autoimmune diseases

MEDI 227

Philip S. Low, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, Chrystal M Paulos, chrystal_paulos@nih.gov, Surgery Branch, National Cancer Institute/National Institute of Health, Building 10, Room 2B42, Bethesda, MD 20892, and Bindu Varghese, varghesb@purdue.edu, Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907.
Activated (but not quiescent) macrophages release multiple mediators of inflammation including TNF-alpha, IL-1, IL-6, prostaglandins, reactive oxygen species, and numerous degradative enzymes. Activated macrophages (but not quiescent macrophages or most other normal cells) also express elevated numbers of folate receptors (FR) that allow selective targeting of folate-linked drugs/imaging agents to the same cells. Because many inflammatory and autoimmune diseases, including rheumatoid arthritis, atherosclerosis, stroke, psoriasis, Crohn's disease, osteoarthritis, ischemia/reperfusion injury, glomerulonephritis, lupus, and sarcoidosis are characterized by significant activated macrophage involvement, these same diseases can be imaged and treated by folate-conjugated imaging and therapeutic agents. This seminar will summarize preclinical and clinical progress aimed at exploiting FR targeting to diagnose and treat the aforementioned inflammatory diseases. Because FR targeted drugs avoid uptake by most nonpathologic tissues, toxicity associated with nontargeted anti-inflammatory drugs appears to be largely avoided by folate targeting.
 

Drug Delivery
1:30 PM-4:50 PM, Tuesday, August 21, 2007 BCEC -- 210B, Oral

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007