Pachyonychia Congenita: A Research Agenda Leading to New Therapeutic Approaches

Edel A O'Toole; David P Kelsell; Michael J Caterina; Marianne de Brito; David Hansen; Robyn P Hickerson; Alain Hovnanian; Roger Kaspar; E Birgitte Lane; Amy S Paller; Janice Schwartz; Braham Shroot; Joyce Teng; Matthias Titeux; Pierre A Coulombe; Eli Sprecher

doi:10.1016/j.jid.2023.10.030

Pachyonychia Congenita: A Research Agenda Leading to New Therapeutic Approaches

J Invest Dermatol. 2024 Apr;144(4):748-754. doi: 10.1016/j.jid.2023.10.030. Epub 2023 Dec 15.

Authors

Edel A O'Toole¹, David P Kelsell², Michael J Caterina³, Marianne de Brito², David Hansen⁴, Robyn P Hickerson⁵, Alain Hovnanian⁶, Roger Kaspar⁷, E Birgitte Lane⁸, Amy S Paller⁹, Janice Schwartz¹⁰, Braham Shroot¹¹, Joyce Teng¹², Matthias Titeux¹³, Pierre A Coulombe¹⁴, Eli Sprecher¹⁵

Affiliations

¹ Centre for Cell Biology and Cutaneous Research, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.
² Centre for Cell Biology and Cutaneous Research, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
³ Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah, USA.
⁵ Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, United Kingdom.
⁶ INSERM UMR 1163, Laboratory of genetic skin diseases, Institut Imagine, Université Paris Cité, Paris, France; Department of Genomic Medicine of Rare Diseases, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
⁷ Ayni Therapeutics, Santa Cruz, California, USA.
⁸ A∗STAR Skin Research Laboratories, Skin Research Institute of Singapore, Singapore, Singapore.
⁹ Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
¹⁰ Pachyonychia Congenita Project, Salt Lake City, Utah, USA.
¹¹ Palvella Therapeutics, Wayne, Pennsylvania, USA.
¹² Pediatric Dermatology, Stanford University School of Medicine, Stanford, California, USA.
¹³ INSERM UMR 1163, Laboratory of genetic skin diseases, Institut Imagine, Université Paris Cité, Paris, France.
¹⁴ Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
¹⁵ Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Human Molecular Genetics and Biochemistry, School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Electronic address: elisp@tlvmc.gov.il.

PMID: 38099888
DOI: 10.1016/j.jid.2023.10.030

Abstract

Pachyonychia congenita (PC) is a dominantly inherited genetic disorder of cornification. PC stands out among other genodermatoses because despite its rarity, it has been the focus of a very large number of pioneering translational research efforts over the past 2 decades, mostly driven by a patient support organization, the Pachyonychia Congenita Project. These efforts have laid the ground for innovative strategies that may broadly impact approaches to the management of other inherited cutaneous and noncutaneous diseases. This article outlines current avenues of research in PC, expected outcomes, and potential hurdles.

Keywords: Drug repurposing; Genodermatosis; Keratoderma; Nails; Pachyonychia congenita.

Publication types

Review

MeSH terms

Administration, Cutaneous
Apoptosis
Cell Differentiation
Humans
Keratoderma, Palmoplantar* / genetics
Mutation
Pachyonychia Congenita* / diagnosis
Pachyonychia Congenita* / genetics
Pachyonychia Congenita* / therapy