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Ian Zagon, MS, PhD

Ian Zagon, MS, PhD

Distinguished Professor, Department of Neural and Behavioral Sciences
Penn State Neuroscience Institute
Scientific Program:Next-Generation Therapies

Research Interests

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.

  • Opioid Analgesics
  • Intercellular Signaling Peptides and Proteins
  • Naltrexone
  • methionine-enkephalin receptor
  • Growth
  • Neoplasms
  • Enkephalins
  • Brain
  • Opioid Receptors
  • Therapeutics
  • Cell Proliferation
  • Narcotic Antagonists

Recent Publications


Diaz, D, Sassani, JP, Zagon, IS & McLaughlin, P 2024, 'Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats', Experimental Biology and Medicine, vol. 249, 10175.


McLaughlin, PJ, Sassani, JW & Zagon, IS 2023, 'Safety study of topical naltrexone therapy for diabetic skin wounds is confirmed in Göttingen mini-pigs', Drug Development Research, vol. 84, no. 6, pp. 1279-1284.


McLaughlin, PJ, Odom, LB, Arnett, PA, Orehek, S, Thomas, GA & Zagon, IS 2022, 'Low-dose naltrexone reduced anxiety in persons with multiple sclerosis during the COVID-19 pandemic', International Immunopharmacology, vol. 113, 109438.


McLaughlin, PJ, Sassani, J, Purushothaman, I & Zagon, IS 2021, 'Naltrexone blockade of OGFr enhances cutaneous wound closure in diabetic rats', Medicine in Drug Discovery, vol. 11, 100098.
Purushothaman, I, Zagon, IS, Sassani, JW & McLaughlin, PJ 2021, 'Ocular surface complications in diabetes: The interrelationship between insulin and enkephalin', Biochemical Pharmacology, vol. 192, 114712.
Purushothaman, I, Zagon, IS, Sassani, J & McLaughlin, PJ 2021, 'Ocular surface complications result from dysregulation of the OGF-OGFr signaling pathway in female diabetic rats', Experimental and Therapeutic Medicine, vol. 22, no. 1, 687.
Purushothaman, I, Zagon, IS, Sassani, JW, Zhou, S & McLaughlin, PJ 2021, 'Sex differences in the magnitude of diabetic ocular surface complications: Role of serum OGF', Physiology and Behavior, vol. 237, 113436.
Patel, C, Zagon, IS, Pearce-Clawson, M & McLaughlin, PJ 2022, 'Timing of treatment with an endogenous opioid alters immune response and spinal cord pathology in female mice with experimental autoimmune encephalomyelitis', Journal of Neuroscience Research, vol. 100, no. 2, pp. 551-563.
Patel, C, Thomas, G, Zomorodi, N, Zagon, IS & McLaughlin, PJ 2021, 'β-endorphin and opioid growth factor as biomarkers of physical ability in multiple sclerosis', Multiple Sclerosis and Related Disorders, vol. 50, 102868.


Zagon, IS, Sassani, JW, Purushothaman, I & McLaughlin, PJ 2021, 'Blockade of OGFr delays the onset and reduces the severity of diabetic ocular surface complications', Experimental Biology and Medicine, vol. 246, no. 5, pp. 629-636.
Zagon, IS, Sassani, JW, Purushothaman, I & McLaughlin, PJ 2020, 'Dysregulation of the OGF–OGFr pathway correlates with elevated serum OGF and ocular surface complications in the diabetic rat', Experimental Biology and Medicine, vol. 245, no. 15, pp. 1414-1421.
Patel, C, Meadowcroft, MD, Zagon, IS & McLaughlin, PJ 2020, '[Met5]-enkephalin preserves diffusion metrics in EAE mice', Brain Research Bulletin, vol. 165, pp. 246-252.