Thyroid-associated ophthalmopathy (TAO), the ocular manifestation of Graves' disease, is a process in which orbital connective tissues and extraocular muscles undergo inflammation and remodeling. The condition seems to result from autoimmune responses to antigens shared by the thyroid and orbit. The thyrotropin receptor (TSHR), expressed at low levels in orbital tissues, is a leading candidate antigen. Recent evidence suggests that another protein, the insulin-like growth factor-I receptor (IGF-IR), is overexpressed in TAO, and antibodies against IGF-IR have been detected in patients with the disease. Furthermore, TSHR and IGF-IR form a physical and functional complex, and signaling initiated at TSHR requires IGF-IR activity. Identification of therapy for this rare disease has proven challenging and currently relies on nonspecific and inadequate agents, thus representing an important unmet need. A recently completed therapeutic trial suggests that inhibiting IGF-IR activity with a monoclonal antibody may be an effective and safe treatment for active TAO.
Keywords: Graves’ disease; autoimmune; monoclonal antibody; signaling.