Yiumo Michael ChanAnnJi Pharmaceutical Co. Ltd, Taiwan
Title: Androgen receptor, oxidative stress and inflammation at the crossroads of skin diseases
Skin represents one of the largest organs in humans and is constantly under the insult of oxidative stress and inflammation. Although many inflammatory and autoimmune skin diseases can be managed by immunosuppressants and corticosteroids, the long-term use remains a major safety concern in the medical practice. Here, we present evidence that a class of non-steroid compounds, known as Nrf2 (nuclear factor erythroid 2-related factor 2) activators can be developed to treat different skin diseases associated with increased oxidant stress and inflammatory responses. Nrf2 is a well characterized master transcription factor to regulate cellular antioxidant response. These novel compounds were designed based on structural modifications of the natural product, curcumin. In additional to inducing robust antioxidant response through Nrf2, our in vitro studies demonstrated that these compounds have additional unique properties of suppressing proinflammatory cytokines and enhancing the degradation of androgen receptor, possibly through proteasome- and heat shock protein-mediated pathways. These compounds were developed into different formulations for both oral and topical administrations. The oral formulation is currently at the early clinical phase for treatment of a rare poly-Q disease known as spinal and bulbar muscular atrophy whereas the topical formulation has completed a global Phase 2 clinical trial of acne vulgaris. Our preclinical studies in cell and animal models have supported the therapeutic potential of these novel Nrf2 activators in different skin disease models, such as keloid. As a result, this class of novel Nrf2 activators could be promising therapeutic agents to treat in treating a variety of skin conditions, including androgen-associated skin diseases, inflammatory skin diseases, wound healing, hair loss, and skin aging.
Yiumo Michael Chan’s research areas include rare diseases research and drug development of small molecules. Dr. Chan received his B.Sc. and Ph.D. degrees from the University of Chicago and completed his post-doctoral training at Harvard Medical School. Dr. Chan has extensive research experience in academia and held a faculty position at Geisinger Medical Center, PA. He is a scientific leader in rare and neuromuscular diseases with a proven record in publication and discovery, including the identification of the genetic basis of Weber-Cockayne epidermolysis bullosa simplex. Dr. Chan also serves several scientific advisory boards for different patient organizations of rare diseases. In industry, Dr. Chan has demonstrated a successful track record in drug development of small molecules. He was responsible for translational programs in neuromuscular and neurodevelopmental diseases at Ultragenyx, CA, including the GNE Myopathy program which advanced from preclinical stage to Phase III clinical trial. Dr. Chan is currently the Vice President of Research and Translational Medicine at AnnJi Pharmaceutical, a clinical stage biopharmaceutical company specializing in development of novel treatments for neglected diseases in neurology and dermatology. He has led more than 6 Phase I/II clinical studies for common and rare skin diseases.