Article
Multidisciplinary Sciences
Kaori Soma, Kengo Watanabe, Masanori Izumi
Summary: Pseudoxanthoma elasticum (PXE) is a genetic disorder with no effective treatment. In this study, the TNAP inhibitor DS-1211 showed potential anticalcification effects in PXE mouse models, suggesting it as a potential therapeutic drug for PXE.
SCIENTIFIC REPORTS
(2022)
Article
Dermatology
Ida Joely Jacobs, Diana Li, Mattias E. Ivarsson, Jouni Uitto, Qiaoli Li
Summary: The study demonstrated that INS-3001 effectively prevents and stabilizes ectopic calcification in a mouse model of Pseudoxanthoma elasticum (PXE). Different doses of INS-3001 showed dose-dependent inhibition of calcification, with both subcutaneous injections and osmotic pump implantation proving effective in treatment.
EXPERIMENTAL DERMATOLOGY
(2021)
Article
Dermatology
Ida Joely Jacobs, Zhiliang Cheng, Douglas Ralph, Kevin O'Brien, Lisa Flaman, Jennifer Howe, David Thompson, Jouni Uitto, Qiaoli Li, Yves Sabbagh
Summary: This study found that restoring plasma PPi levels can prevent ectopic calcification in a mouse model of Pseudoxanthoma elasticum (PXE). INZ-701 increases plasma ENPP1 activity and PPi levels, leading to significantly reduced calcification in the muzzle skin of the mice.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elise Bouderlique, Lukas Nollet, Emmanuel Letavernier, Olivier M. Vanakker
Summary: In this proof-of-concept study, the anticalcifying effect of minocycline was validated in Abcc6(-/-) mice for the first time, suggesting it as a promising therapeutic compound for PXE patients due to its favorable safety profile in humans and low cost as a generic drug.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Dermatology
Aiping Zheng, Patrick H. Thibodeau
Summary: Significant progress has been made in understanding pseudoxanthoma elasticum (PXE), and researchers have proposed a novel in vivo model for characterizing and annotating ABCC6 variants.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Dermatology
Hongbin Luo, Masoomeh Faghankhani, Yi Cao, Jouni Uitto, Qiaoli Li
Summary: In the past two decades, significant progress has been made in understanding the molecular basis and pathomechanistic details of pseudoxanthoma elasticum (PXE). Genetic modifiers have been identified to explain the phenotypic heterogeneity of PXE, in addition to pathogenic variants in the ABCC6 gene. The genetic complexity of PXE is further complicated by PXE-like phenotypes caused by variants in other ectopic mineralization-associated genes.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Dermatology
Jianhe Huang, Douglas Ralph, Federica Boraldi, Daniela Quaglino, Jouni Uitto, Qiaoli Li
Summary: The DNA damage response (DDR) and poly(ADP-ribose) (PAR) pathways are involved in the ectopic calcification in pseudoxanthoma elasticum (PXE). Inhibition of PAR polymerase 1 (PARP1) and minocycline treatment can reduce calcification. These findings suggest that local DDR/PAR signaling contributes to the pathogenesis of PXE and its inhibition may be a promising treatment strategy for ectopic calcification in PXE.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Medicine, General & Internal
Eszter Kozak, Jonas W. Bartstra, Pim A. de Jong, Willem P. T. M. Mali, Krisztina Fulop, Natalia Tokesi, Viola Pomozi, Sara Risseeuw, Jeannette Ossewaarde-van Norel, Redmer van Leeuwen, Andras Varadi, Wilko Spiering
Summary: ABCC6 gene mutations in patients with pseudoxanthoma elasticum (PXE) were found to be associated with lower plasma inorganic pyrophosphate (PPi) levels. However, no association between PPi levels and PXE phenotypes or ABCC6 genotypes was found in this study.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Medicine, General & Internal
Hongbin Luo, Qiaoli Li, Yi Cao, Jouni Uitto
Summary: Pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI) and arterial calcification due to CD73 deficiency (ACDC) are heritable ectopic mineralization disorders characterized by reduced plasma levels of inorganic pyrophosphate (PPi). Current research efforts aim to develop treatments for these conditions by normalizing PPi plasma levels or preventing calcium hydroxyapatite deposition independently of PPi.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
A. Legrand, C. Pujol, C. M. Durand, A. Mesnil, I. Rubera, C. Duranton, S. Zuily, A. B. Sousa, M. Renaud, J. L. Boucher, N. Pietrancosta, S. Adham, C. Orssaud, C. Marelli, C. Casali, L. Ziccardi, N. Villain, C. Ewenczyk, A. Durr, C. Mignot, G. Stevanin, C. Billon, M. Hureaux, X. Jeunemaitre, C. Goizet, J. Albuisson
Summary: A study identified CYP2U1 pathogenic variants in PXE patients with neurological symptoms who were unresolved by ABCC6 genetic screening, expanding the phenotype of SPG56 and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored further to understand their respective roles and potential interaction in ectopic mineralization.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Dermatology
Eszter Kozak, Krisztina Fulop, Natalia Tokesi, Nidhi Rao, Qiaoli Li, Sharon F. Terry, Jouni Uitto, Xiaoming Zhang, Cyrus Becker, Andras Varadi, Viola Pomozi
Summary: PXE is a rare hereditary multisystem disorder affecting elastic fibers in the skin, eyes, and cardiovascular system. Research has shown that orally administered pyrophosphate compounds can inhibit ectopic calcification, providing a crucial foundation for potential clinical trials involving oral PPi in the future.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Medicine, General & Internal
Federica Boraldi, Vittoria Murro, Francesco Demetrio Lofaro, Dario Pasquale Mucciolo, Sonia Costa, Laura Pavese, Daniela Quaglino
Summary: ABCC6 rare sequence variants were found throughout the entire gene in a cohort of Italian PXE patients. The severity of clinical phenotype in PXE patients was found to be age-dependent, with in-depth ophthalmological examinations providing insight into disease progression and allowing for better patient stratification.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Dermatology
Lukas Nollet, Matthias Van Gils, Andy Willaert, Paul J. Coucke, Olivier M. Vanakker
Summary: Excessive DDR/PARP1 signaling is involved in the pathogenesis of PXE, contributing to aberrant mineralization. Treatment with the PARP1 inhibitor minocycline attenuates this signaling and reduces ectopic calcification. This study provides new insights for the treatment of PXE.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Cell Biology
David Czimer, Klaudia Porok, Daniel Csete, Zsolt Gyure, Viktoria Lavro, Krisztina Fulop, Zelin Chen, Hella Gyergyak, Gabor E. Tusnady, Shawn M. Burgess, Attila Mocsai, Andras Varadi, Mate Varga
Summary: Calcification is a significant health issue associated with aging, cancer, and autoimmune diseases, with both environmental and genetic factors at play. Understanding the phenomenon is essential for developing effective therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease without a cure, but research shows that zebrafish could serve as a new model for studying the disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Klara Farkas, Norbert Kiss, Viktoria Szabo, Miklos Resch, Rita Vamos, Agnes Borbandy, Ilona Nagy Aniko, Astrid Apor, Tamas Aranyi, Flora Szeri, Norbert Wikonkal, Zsolt Nagy Zoltan, Bela Merkely, Marta Medvecz
Summary: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder caused by ABCC6 gene mutations. It leads to ectopic mineralization and deposits of calcium-salt crystals in the skin, eyes, and blood vessels. The clinical symptoms are diverse and require collaboration between multiple specialists for accurate diagnosis and management. Early diagnosis and coordination of care are crucial for optimal patient outcomes.
Article
Pathology
Qiujie Jiang, Reid Oldenburg, Satoru Otsuru, Alix E. Grand-Pierre, Edwin M. Horwitz, Jouni Uitto
AMERICAN JOURNAL OF PATHOLOGY
(2010)
Review
Biochemistry & Molecular Biology
Laure Guenin-Mace, Reid Oldenburg, Fabrice Chretien, Caroline Demangel
CELLULAR AND MOLECULAR LIFE SCIENCES
(2014)
Article
Dermatology
Reid P. Oldenburg, Monica S. Liu, Michael S. Kolodney
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2008)
Article
Infectious Diseases
Richard O. Phillips, Fred S. Sarfo, Jordi Landier, Reid Oldenburg, Michael Frimpong, Mark Wansbrough-Jones, Kabiru Abass, William Thompson, Mark Forson, Arnaud Fontanet, Fatoumata Niang, Caroline Demangel
PLOS NEGLECTED TROPICAL DISEASES
(2014)