A $5 million, five-year award establishes the Consortium for Hereditary Epidermal Differentiation Disorders (CHEDD) within the NIH Rare Diseases Clinical Research Network
CHICAGO and NEW HAVEN, Conn. — Northwestern University Feinberg School of Medicine and Yale School of Medicine will jointly lead a new national research consortium dedicated to epidermal differentiation disorders (EDDs), a large group of rare, inherited skin diseases formerly known as the ichthyoses and palmoplantar keratodermas.
The Consortium for Hereditary Epidermal Differentiation Disorders (CHEDD) is funded by a five-year award providing $5 million in direct research costs from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health (NIH), and joins the NIH Rare Diseases Clinical Research Network (RDCRN).
The patient voice has been incorporated throughout the development of CHEDD, including input from several members of The Foundation for Ichthyosis & Related Skin Types (FIRST) Board of Directors, Christopher Boynton (FIRST CEO) and other patients and families affected by these disorders. Their perspectives are helping to inform the questions being asked, the outcomes being considered and how the research can address the needs of people living with these conditions. FIRST is also providing funding to support a portion of the research conducted through this effort. The patient community will also be needed as this project progresses.
CHEDD is led by Amy S. Paller, MD, Walter J. Hamlin Professor of Dermatology, professor of pediatrics, and chair of the Department of Dermatology at Northwestern University Feinberg School of Medicine, and Keith A. Choate, MD, PhD, Aaron B. and Marguerite Lerner Professor and Chair of Dermatology, professor of genetics and of pathology, and associate dean for physician-scientist development at Yale School of Medicine. The consortium brings together seven clinical sites, patient advocacy organizations, and the RDCRN’s Data Management and Coordinating Center to study these conditions at a scale no single center could achieve.
In addition to Northwestern and Yale, CHEDD clinical sites include Stanford University (site lead Joyce Teng MD, PhD), the University of California San Diego and Rady Children’s Hospital (Lawrence Eichenfield, MD), the University of Colorado (Anna Bruckner, MD), the Medical University of South Carolina (Lara Wine Lee, MD, PhD), and The University of Texas at Austin and Dell Children’s Medical Center (Moise Levy, MD).
Epidermal differentiation disorders is the umbrella term, adopted in a recent international consensus classification, for the group of genetic skin conditions that result from variants in genes encoding skin structural proteins, lipid-metabolism enzymes and transporters, channels, and other components required for a healthy skin barrier. They manifest as skin thickening, scaling, and redness. The ichthyoses, palmoplantar keratodermas, and related disorders of epidermal differentiation are subsets.
“For many families living with these disorders, the most pressing questions — what will happen over time, and what treatment will help my child — have not had adequate answers,” said Choate.
“By bringing genetic diagnosis, careful long-term follow-up, and new molecular tools together across many centers, CHEDD will let us learn how these diseases unfold and match patients to therapies that target the underlying cause.”
Consortium leadership Paller directs CHEDD’s Administrative Core and leads Project 2; Choate serves as associate director of the administrative core and leads Project 3 with co-investigator Mark Gerstein, PhD, of Yale. Joyce Teng, MD, PhD, of Stanford leads Project 1. Lara Wine Lee, MD, PhD, of the Medical University of South Carolina directs the Pilot-Feasibility Core, which will fund new studies from investigators across and beyond the consortium, and Jon Dyer, MD, of the University of Missouri directs the Career Enhancement Core, which supports clinicians and clinician-scientists entering the field.
Additional consortium leaders include Stephanie M. Rangel, PhD, of Northwestern as program manager and director of clinical research integration and compliance; Hongyu Zhao, PhD, of Yale directing statistics and data analytics; Gerstein directing biomarker data analysis and integration; and Rinad Beidas, PhD, of Northwestern directing dissemination and implementation.
Three coordinated research projects
Project 1 will establish a longitudinal registry and natural-history study, pairing genetic diagnosis with standardized clinical assessments over time to define how each EDD subtype progresses and to identify outcome measures for future clinical trials.
Project 2 is a clinical trial of erlotinib, an oral targeted medication, in K6-pEDD (Pachyonychia Congenita) and K1, K10-EDD (ClinicalTrials.gov NCT06545695), testing whether blocking an overactive growth-signaling pathway in the skin can improve disease.
Project 3 will integrate spatial transcriptomics, blood gene-expression profiling, proteomics, lipidomics, and skin microbiome analysis to map the molecular changes behind each disorder and to identify biomarkers of disease activity and treatment response.
The consortium also includes an Administrative Core, a Pilot-Feasibility Core that will fund new studies, and training/career-enhancement program for early-career investigators. Data and biospecimens collected through CHEDD will be shared with the research community through the RDCRN and NIH data repositories.
“Children and adults with epidermal differentiation disorders deserve the same rigorous, evidence-based care that we expect for more common diseases,” said Paller. “This consortium gives us the infrastructure to run the natural-history studies and clinical trials that regulators and families need, and to do it together with the patient community from the start.”
About epidermal differentiation disorders
Epidermal differentiation disorders is the umbrella term, adopted in a recent international consensus classification, for the group of genetic skin conditions previously called the ichthyoses, palmoplantar keratodermas, and related disorders of epidermal differentiation. They result from variants in genes encoding skin structural proteins, lipid-metabolism enzymes and transporters, channels, and other components required for a healthy skin barrier.
About the Rare Diseases Clinical Research Network
The Rare Diseases Clinical Research Network (RDCRN), established under the Rare Diseases Act of 2002, supports clinical research and collaboration across consortia studying more than 280 rare diseases at clinical sites around the world, in partnership with patients and patient advocacy groups.
Research reported in this release is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number U54AR089183. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
