Philip S. Low

Next Generation Targeted Therapeutics

Novel imaging and therapeutic agents for autoimmune diseases

Imaging of human hands

The National Institute of Allergy and Infectious Diseases estimates that the cost of treating autoimmune diseases is >$100 billion annually in the US. In our search for a pathologic cell type that might contribute prominently to such diseases, we concluded that the activated macrophage played a critical role in the progression of more autoimmune diseases than any other cell type. Recognizing that the activated (but not resting) macrophage expresses a folate receptor that can readily be exploited for targeted drug delivery, we undertook to develop folate-targeted drugs for imaging and therapy of such autommune diseases as rheumatoid arthritis, pulmonary fibrosis, Crohn’s disease, scleroderma, multiple sclerosis, sarcoidosis, ulcerative colitis, psoriasis, uveitis, and Sjogren’s disease, etc.). We now have a “toolbox” of folate-targeted therapeutic agents that can reprogram either M1→M2 or M2→M1 macrophages and have shown that these reagents can profoundly suppress the symptoms of many animal models of autoimmune diseases. We have also developed folate-targeted SPECT, PET, and fluorescent imaging agents for diagnosis and monitoring autoimmune diseases.