Hydrogel Therapies for Alopecia Areata

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Proposal Summary/Abstract Candidate: Dr. Leo Wang holds a BA, MS, MD, and PhD from the University of Pennsylvania, where he is currently completing dermatology residency and a postdoctoral fellowship. Since 2018, Dr. Wang has been working with Dr. George Cotsarelis, MD, with a primary focus on biomaterial-based approaches for addressing hair and skin disorders. Support from a K08 award will strategically position Dr. Wang to become an R01-funded investigator and a leader in the fields of biomaterials and dermatology. Environment: The mentor, Dr. Cotsarelis, is the Milton Bixler Hartzell Professor and Chair of Dermatology. He is internationally recognized for expertise in hair disorders, animal models of skin diseases, and therapeutic development. Dr. Cotsarelis boasts a remarkable track record as a mentor, including for previous K08 awardees. Dr. Cotsarelis will be joined by a mentoring committee comprising experts in relevant domains. Dr. Christopher Madl, PhD, Assistant Professor of Materials Science and Engineering, is a leading authority in hydrogel biomaterials, who will provide expertise in synthesis, characterization, and applications. Dr. David Margolis, MD, PhD, Gerald Lazarus Professor of Dermatology, is a world-renowned specialist in clinical trials, biostatistics, and biomaterials for clinical translation, who will advise animal studies. Dr. John Wherry, PhD, the Richard and Barbara Schiffrin Professor and Chair, Department of Systems Pharmacology & Translational Therapeutics, will provide mentorship in immunologic analysis of the alopecia areata model. The K08 proposal encompasses training in engineering, mass spectrometry imaging techniques, in vivo models, accompanied by coursework. The University of Pennsylvania offers an outstanding Dermatology faculty, fostering opportunities for collaboration, and boasts NIAMS P30-supported core facilities and other cores to support the proposed studies. Research: Alopecia areata (AA) is an autoimmune disease caused by a cytotoxic T cell-mediated inflammatory response in the hair bulb leading to nonscarring hair loss. Janus kinase (JAK) inhibitors have been approved clinically for use, but their utility is limited by the risk of systemic toxicity, necessitating innovative delivery methods. Injectable hydrogels offer a promising solution by enabling local and sustained drug delivery, concentrating the medication in the skin while minimizing systemic absorption. This research proposal aims to harness the nitrile group present in baricitinib, an FDA-approved oral JAK inhibitor, to form a dynamic covalent thioimidate bond with a thiolated hydrogel to treat alopecia areata. The proposal will test the hypothesis that thioimidates can sustain drug delivery for 12 weeks after injection, ensuring high local bioavailability in human skin xenografts, low systemic absorption, and effectiveness in preventing and treating alopecia areata. This technology has significant translational potential and can be readily utilized by dermatologists and other healthcare providers for various skin and systemic disorders that converge on JAK signaling.