RARE DISEASE
Pseudoxanthoma elasticum
Pseudoxanthoma elasticum
Pseudoxanthoma elasticum
Synonyms: Gronblad-Strandberg-Touraine syndrome, PXE
Synonyms: Gronblad-Strandberg-Touraine syndrome, PXE
Synonyms: Gronblad-Strandberg-Touraine syndrome, PXE
Drug discovery
3
drugs
With orphan designations
Overview
Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by ABCC6 mutations, leading to ectopic mineralization of elastic fibers in skin, eyes, and cardiovascular tissues. Clinical features include yellowish skin papules, angioid streaks with risk of choroidal neovascularization, and vascular complications like claudication. Diagnosis combines clinical findings, histopathology (calcified elastic fibers), and genetic testing. Management focuses on symptom mitigation, as no disease-modifying therapies exist [1][2][4][17].
Therapies
Ocular: Intravitreal anti-VEGF agents (e.g., bevacizumab) for choroidal neovascularization [4][11][18].
Cardiovascular: Lipid-lowering agents, blood pressure control, and vascular surgery for severe arteriosclerosis [2][16][17].
Symptomatic**: Cosmetic surgery for skin laxity; magnesium supplementation and bisphosphonates under investigation [6][16][20].
Categories: rare cardiac diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare neurological diseases, rare ophthalmic disorders, rare renal diseases, rare skin diseases, rare transplant-related disorders
Research Papers
296 drug discovery papers about Pseudoxanthoma elasticum, with 5 first-in-class and 8 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
296 drug discovery papers about Pseudoxanthoma elasticum, with 5 first-in-class and 8 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-10 | Ectopic calcification is inhibited by minocycline also in PARP-1-independent in vitro models
Ectopic calcification (EC) is a still untreatable hallmark of genetic and acquired diseases. Recent findings suggested that minocycline (Mi) retains several biological impacts beyond its antibiotic function, including anti-inflammatory and antioxidant effects, modulation of the nucleus-mitochondria crosstalk, inhibition of the stress-induced over-activation of the poly(ADP-ribose) polymerase-1 (PARP-1) involved in DNA repair and possibly in EC. Interestingly, some of these pathways are involved in the pathogenesis of Pseudoxanthoma elasticum (PXE), a genetic disease considered a paradigm of EC. Notably, data have been provided indicating an association between anti-calcifying effects of Mi and PARP-1 inhibition, although the involved pathways remain unclear. Therefore, we have investigated through integrated approaches which molecular pathways can be involved in the proposed anti-calcifying potential of Mi. This study shows that Mi inhibits mineralization acting both in the extracellular (i.e., acellular model of coacervated elastin fibrils) and in the intracellular (i.e., cultured PXE dermal fibroblasts) environments. Results support and broaden the calcification inhibitory capability of Mi suggesting that, also in PARP-1 independent in vitro models of calcification, mineral deposition can be inhibited through the calcium chelating properties of the drug and the action on mitochondria mainly preserving Δψ m although oxidative stress is not affected.
2026-07-29 | Phosphocitrate Is Superior to Pyrophosphate in Preventing Soft Connective Tissue Calcification in a Mouse Model of Pseudoxanthoma Elasticum.
Pseudoxanthoma elasticum (PXE) is a rare inherited disorder characterized by progressive ectopic calcification of soft connective tissues, including skin, arteries, and eyes, leading to significant morbidity. PXE results from loss of functional ABCC6, a liver specific ATP efflux conduit. Reduced ATP release into the circulation limits its conversion into AMP and the mineralization inhibitor pyrophosphate (PPi). Consequently, low plasma PPi levels drive ectopic calcification in PXE. Although oral PPi supplementation can inhibit ectopic calcification in Abcc6-/- mice, impractically high doses are needed, due to its rapid hydrolysis in the gastrointestinal tract. Here, we evaluated phosphocitrate, an exceedingly more potent mineralization inhibitor, in vitro and in Abcc6-/- mice. In ATDC5 cells, 1 μM phosphocitrate significantly inhibited mineralization following induction, comparable to approximately tenfold higher concentrations of PPi. In vivo, daily intraperitoneal administration of phosphocitrate (4.7 μmol/kg bw) markedly reduced calcification in muzzle skin and kidneys, whereas an at least fivefold higher dose of PPi was needed to achieve a similar effect. Oral administration required substantially higher doses of both compounds (~2.4 mmol/kg bw), but PC remained more effective than PPi at inhibiting soft tissue calcification in Abcc6-/- mice. Importantly, unlike PPi, oral phosphocitrate did not adversely affect skeletal strength or stiffness, even at supraphysiological doses. In summary, phosphocitrate is a more potent inhibitor of ectopic calcification than PPi in Abcc6-/- mice. While optimization of oral delivery remains necessary, its increased potency supports the potential of alternative administration routes, including subcutaneous delivery, as a practical therapeutic strategy for PXE.
2026-07-27 | SCAMP – an open-source tool for the quantification of calcification in fish larvae
Abstract Quantifying skeletal mineralization phenotypes in larval fish is complicated by the natural curvature of the notochord and by sample-to-sample variability in orientation, staining and imaging. Consequently, many studies rely on summary measures such as vertebral counts or total stain intensity. Here we present SCAMP (Spinal Calcification & Mineralization Profiler), an open-source, GUI-based Python tool that computationally straightens the curved notochord of Alizarin Red S-stained fish larvae and generates standardized mineralization profiles along the spinal axis. This approach reduces positional and shape variability, allowing direct, quantitative comparison of calcification patterns within and between experimental cohorts, without requiring programming expertise. We validate SCAMP using a zebrafish model of Pseudoxanthoma elasticum ( abcc6a elu15/elu15 ), recovering genotype-specific differences in the intensity, extent and spatial distribution of ectopic calcification. Using SCAMP, we further show that inorganic pyrophosphate (PPi) supplementation of the medium suppresses ectopic notochord calcification, alters the anterior–posterior distribution of mineralized regions in homozygous mutants, and promotes mineralization at physiological vertebral sites. We also show that methylene blue, a routine antifungal additive in fish medium, reduces baseline calcification, with the most pronounced effects observed in heterozygous controls. SCAMP is freely available and has the potential to be adapted to other fish species used in skeletal and mineralization research.
2026-06-15 | Chronic Total Occlusion Recanalization in a 14-Year-Old Girl With Pseudoxanthoma Elasticum: IVUS-Guided Stentless Strategy.
Pseudoxanthoma elasticum (PXE) is a hereditary disorder causing progressive arterial mineralization that may cause premature coronary disease in children. A 14-year-old girl with exertional angina since age 8 was diagnosed with PXE after her mother used an artificial intelligence tool to identify skin lesions. Coronary imaging revealed mid-left anterior descending artery chronic total occlusion without CT macrocalcification. Intravascular ultrasound (IVUS) demonstrated concentric high-echoic wall thickening without acoustic shadowing, consistent with mineralized elastic lamina rather than atherosclerosis. A stentless drug-coated balloon strategy was chosen. At 10 months, she was asymptomatic with sustained left anterior descending artery patency by scheduled angiography. This is the first reported IVUS-guided chronic total occlusion recanalization in a pediatric PXE patient, illustrating how intravascular imaging can characterize disease biology and guide individualized device selection. In children with unexplained exertional symptoms and skin lesions, PXE should be considered. When IVUS identifies a nonatherosclerotic substrate, a stentless strategy may preserve vessel growth potential.
2026-04-25 | Asymmetric functional evolution of bilateral giant angioid streaks after 14 years of follow-up: A case report
• Bilateral giant subfoveal angioid streaks with pseudoxanthoma elasticum • High risk of choroidal neovascularization and severe hemorrhagic complications • 14-year follow-up showing asymmetric functional evolution between both eyes • Earlier switch to treat-and-extend regimen was associated with preserved vision Angioid streaks are rare, dark red, radiating fundus lesions surrounding the optic nerve head caused by breaks in Bruch's membrane. They predispose to choroidal neovascularization and recurrent hemorrhages requiring proactive management. We report a 44-year-old pseudoxanthoma elasticum patient with bilateral, atypical macular angioid streaks and a 14-year follow-up. In 2011, fundus examination revealed horizontal angioid streaks traversing the macula bilaterally without evidence of choroidal neovascularization; best-corrected visual acuity was 10/10 Parinaud 2 both eyes. The left eye subsequently developed neovascularization complicated by macular hemorrhages. Within two years, bilateral neovascularization with recurrent macular hemorrhages developed, prompting transition from a PRN to a treat-and-extend regimen. After 11 years of intravitreal ranibizumab therapy, the right eye maintained baseline visual acuity, while the left eye progressively declined to 1/10 (Parinaud 16) due to fibrotic sequelae. This case illustrates an interesting angioid streak pattern, characterized by giant horizontal streaks crossing the fovea, an anatomical configuration associated with particularly high risk of choroidal neovascularization and submacular hemorrhages. The 14-year follow up demonstrates the limitations of a pro re nata regimen in these high-risk presentations, as delayed transition to treat-and-extend failed to prevent subfoveal fibrosis and severe visual loss in the left eye. Conversely, earlier treatment initiation and earlier transition to treat-and-extend protocol was associated with preserved vision in the right eye. This case could suggest that a proactive approach may optimize visual outcomes as in age related macular degeneration. There is a lack of guidelines and studies on this therapeutic strategy. Close monitoring, assessment with optical coherence tomography angiography, and preventive education are essential, particularly regarding the risk of neovascularization and hemorrhage in patients with foveal-spanning angioid streaks. A proactive regimen may represent a more suitable and effective option for these patients when complications appear.
2026-08-10 | Ectopic calcification is inhibited by minocycline also in PARP-1-independent in vitro models
Ectopic calcification (EC) is a still untreatable hallmark of genetic and acquired diseases. Recent findings suggested that minocycline (Mi) retains several biological impacts beyond its antibiotic function, including anti-inflammatory and antioxidant effects, modulation of the nucleus-mitochondria crosstalk, inhibition of the stress-induced over-activation of the poly(ADP-ribose) polymerase-1 (PARP-1) involved in DNA repair and possibly in EC. Interestingly, some of these pathways are involved in the pathogenesis of Pseudoxanthoma elasticum (PXE), a genetic disease considered a paradigm of EC. Notably, data have been provided indicating an association between anti-calcifying effects of Mi and PARP-1 inhibition, although the involved pathways remain unclear. Therefore, we have investigated through integrated approaches which molecular pathways can be involved in the proposed anti-calcifying potential of Mi. This study shows that Mi inhibits mineralization acting both in the extracellular (i.e., acellular model of coacervated elastin fibrils) and in the intracellular (i.e., cultured PXE dermal fibroblasts) environments. Results support and broaden the calcification inhibitory capability of Mi suggesting that, also in PARP-1 independent in vitro models of calcification, mineral deposition can be inhibited through the calcium chelating properties of the drug and the action on mitochondria mainly preserving Δψ m although oxidative stress is not affected.
2026-07-29 | Phosphocitrate Is Superior to Pyrophosphate in Preventing Soft Connective Tissue Calcification in a Mouse Model of Pseudoxanthoma Elasticum.
Pseudoxanthoma elasticum (PXE) is a rare inherited disorder characterized by progressive ectopic calcification of soft connective tissues, including skin, arteries, and eyes, leading to significant morbidity. PXE results from loss of functional ABCC6, a liver specific ATP efflux conduit. Reduced ATP release into the circulation limits its conversion into AMP and the mineralization inhibitor pyrophosphate (PPi). Consequently, low plasma PPi levels drive ectopic calcification in PXE. Although oral PPi supplementation can inhibit ectopic calcification in Abcc6-/- mice, impractically high doses are needed, due to its rapid hydrolysis in the gastrointestinal tract. Here, we evaluated phosphocitrate, an exceedingly more potent mineralization inhibitor, in vitro and in Abcc6-/- mice. In ATDC5 cells, 1 μM phosphocitrate significantly inhibited mineralization following induction, comparable to approximately tenfold higher concentrations of PPi. In vivo, daily intraperitoneal administration of phosphocitrate (4.7 μmol/kg bw) markedly reduced calcification in muzzle skin and kidneys, whereas an at least fivefold higher dose of PPi was needed to achieve a similar effect. Oral administration required substantially higher doses of both compounds (~2.4 mmol/kg bw), but PC remained more effective than PPi at inhibiting soft tissue calcification in Abcc6-/- mice. Importantly, unlike PPi, oral phosphocitrate did not adversely affect skeletal strength or stiffness, even at supraphysiological doses. In summary, phosphocitrate is a more potent inhibitor of ectopic calcification than PPi in Abcc6-/- mice. While optimization of oral delivery remains necessary, its increased potency supports the potential of alternative administration routes, including subcutaneous delivery, as a practical therapeutic strategy for PXE.
2026-07-27 | SCAMP – an open-source tool for the quantification of calcification in fish larvae
Abstract Quantifying skeletal mineralization phenotypes in larval fish is complicated by the natural curvature of the notochord and by sample-to-sample variability in orientation, staining and imaging. Consequently, many studies rely on summary measures such as vertebral counts or total stain intensity. Here we present SCAMP (Spinal Calcification & Mineralization Profiler), an open-source, GUI-based Python tool that computationally straightens the curved notochord of Alizarin Red S-stained fish larvae and generates standardized mineralization profiles along the spinal axis. This approach reduces positional and shape variability, allowing direct, quantitative comparison of calcification patterns within and between experimental cohorts, without requiring programming expertise. We validate SCAMP using a zebrafish model of Pseudoxanthoma elasticum ( abcc6a elu15/elu15 ), recovering genotype-specific differences in the intensity, extent and spatial distribution of ectopic calcification. Using SCAMP, we further show that inorganic pyrophosphate (PPi) supplementation of the medium suppresses ectopic notochord calcification, alters the anterior–posterior distribution of mineralized regions in homozygous mutants, and promotes mineralization at physiological vertebral sites. We also show that methylene blue, a routine antifungal additive in fish medium, reduces baseline calcification, with the most pronounced effects observed in heterozygous controls. SCAMP is freely available and has the potential to be adapted to other fish species used in skeletal and mineralization research.
2026-06-15 | Chronic Total Occlusion Recanalization in a 14-Year-Old Girl With Pseudoxanthoma Elasticum: IVUS-Guided Stentless Strategy.
Pseudoxanthoma elasticum (PXE) is a hereditary disorder causing progressive arterial mineralization that may cause premature coronary disease in children. A 14-year-old girl with exertional angina since age 8 was diagnosed with PXE after her mother used an artificial intelligence tool to identify skin lesions. Coronary imaging revealed mid-left anterior descending artery chronic total occlusion without CT macrocalcification. Intravascular ultrasound (IVUS) demonstrated concentric high-echoic wall thickening without acoustic shadowing, consistent with mineralized elastic lamina rather than atherosclerosis. A stentless drug-coated balloon strategy was chosen. At 10 months, she was asymptomatic with sustained left anterior descending artery patency by scheduled angiography. This is the first reported IVUS-guided chronic total occlusion recanalization in a pediatric PXE patient, illustrating how intravascular imaging can characterize disease biology and guide individualized device selection. In children with unexplained exertional symptoms and skin lesions, PXE should be considered. When IVUS identifies a nonatherosclerotic substrate, a stentless strategy may preserve vessel growth potential.
2026-04-25 | Asymmetric functional evolution of bilateral giant angioid streaks after 14 years of follow-up: A case report
• Bilateral giant subfoveal angioid streaks with pseudoxanthoma elasticum • High risk of choroidal neovascularization and severe hemorrhagic complications • 14-year follow-up showing asymmetric functional evolution between both eyes • Earlier switch to treat-and-extend regimen was associated with preserved vision Angioid streaks are rare, dark red, radiating fundus lesions surrounding the optic nerve head caused by breaks in Bruch's membrane. They predispose to choroidal neovascularization and recurrent hemorrhages requiring proactive management. We report a 44-year-old pseudoxanthoma elasticum patient with bilateral, atypical macular angioid streaks and a 14-year follow-up. In 2011, fundus examination revealed horizontal angioid streaks traversing the macula bilaterally without evidence of choroidal neovascularization; best-corrected visual acuity was 10/10 Parinaud 2 both eyes. The left eye subsequently developed neovascularization complicated by macular hemorrhages. Within two years, bilateral neovascularization with recurrent macular hemorrhages developed, prompting transition from a PRN to a treat-and-extend regimen. After 11 years of intravitreal ranibizumab therapy, the right eye maintained baseline visual acuity, while the left eye progressively declined to 1/10 (Parinaud 16) due to fibrotic sequelae. This case illustrates an interesting angioid streak pattern, characterized by giant horizontal streaks crossing the fovea, an anatomical configuration associated with particularly high risk of choroidal neovascularization and submacular hemorrhages. The 14-year follow up demonstrates the limitations of a pro re nata regimen in these high-risk presentations, as delayed transition to treat-and-extend failed to prevent subfoveal fibrosis and severe visual loss in the left eye. Conversely, earlier treatment initiation and earlier transition to treat-and-extend protocol was associated with preserved vision in the right eye. This case could suggest that a proactive approach may optimize visual outcomes as in age related macular degeneration. There is a lack of guidelines and studies on this therapeutic strategy. Close monitoring, assessment with optical coherence tomography angiography, and preventive education are essential, particularly regarding the risk of neovascularization and hemorrhage in patients with foveal-spanning angioid streaks. A proactive regimen may represent a more suitable and effective option for these patients when complications appear.
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Drug Discovery Landscape
3 orphan drug designations for Pseudoxanthoma elasticum.
3 orphan drug designations for Pseudoxanthoma elasticum.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Etidronate disodium | small molecules | EMA | 2022-10-11 | — | Haltex Therapeutics B.V. |
Recombinant human ectonucleotide pyrophosphatase/phosphodiesterase 1-Fc (rhENPP1-Fc) enzyme | proteins | FDA | 2021-02-04 | — | Inozyme Pharma, Inc. |
a small molecule tissue-nonspecific alkaline phosphatase inhibitor | small molecules | FDA | 2019-10-07 | — | Daiichi Sankyo, Inc. |
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