The laboratory of Dr. Ian Zagon investigates a novel regulatory pathway, present in a variety of cells and tissues that comprises an endogenous opioid peptide termed opioid growth factor (OGF) and its receptor, OGFr. OGF is an inhibitory growth factor that maintains homeostatic function of cell replication by binding to OGFr, a nuclear-associated receptor. The OGFr gene has been cloned in the Zagon lab, and the human chromosomal location is 20q13.3. OGF binds to OGFr, is transported into the nucleus, upregulates cyclin-dependent inhibitory kinases and subsequently down-regulates the cell cycle.

Currently, the lab’s work is a combination of basic and translational studies focusing on different disease states (i.e., cancer, autoimmune disorders and diabetic complications). Of current interest is the hypothesis that OGF levels are low in autoimmune disorders. Hence, low doses of naltrexone (LDN) that stimulate endogenous OGF production or exogenous OGF treatments are effective at inhibiting inflammatory cell proliferation, thus reversing behavioral deficits and reducing pain. Clinical and animal studies are being used to investigate the role of LDN as a treatment of autoimmune disorders (e.g., Crohn’s, fibromyalgia and multiple sclerosis).

In addition to pursuing the basic biology of the OGF-OGFr axis, the lab is interested in the repercussions of overexpression of OGF and the resulting depressed cell replication often manifested as delayed epithelialization of the cornea following abrasion, dry eye disease, ocular surface hypersensitivity and/or delayed healing of full-thickness cutaneous wounds leading to diabetic foot ulcers. Continuous or total blockade of the OGF-OGFr axis with novel therapeutics has resulted in a reversal of these complications in type 1 diabetic rats, type 2 diabetic mice, and normal animals with specific defects.

Modulation of the OGF-OGFr pathway with receptor antagonists has resulted in a number of therapies that have been patented; several start-up companies have been formed and IP licensed for further commercialization.