Novel Treatments for PXE: Targeting the Systemic and Local Drivers of Ectopic Calcification

Authors

Ida Joely Jacobs, Thomas Jefferson UniversityFollow
Qiaoli Li, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

10-10-2023

Comments

This article is the author's final published version in International Journal of Molecular Sciences, Volume 24, Issue 20, October 2023, Article number 15041.

The published version is available at https://doi.org/10.3390/ijms242015041.

Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland.

Abstract

Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of age, before the development of ectopic calcification, were treated with ETD, Mino, or both for 18 weeks. Micro-computed tomography, histopathologic examination, and quantification of the calcium content in Abcc6-/- mice treated with both ETD and Mino revealed further reduced calcification than either treatment alone. The effects were associated with reduced serum alkaline phosphatase activity without changes in plasma PPi concentrations. These results suggest that ETD and Mino combination therapy might provide an effective therapeutic approach for PXE, a currently intractable disease.

Recommended Citation

Jacobs, Ida Joely and Li, Qiaoli, "Novel Treatments for PXE: Targeting the Systemic and Local Drivers of Ectopic Calcification" (2023). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 246.
https://jdc.jefferson.edu/bmpfp/246

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

37894722

Language

English