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Published on: June 24, 2018
Hexasodium Fytate (SNF472 or CSL525) Inhibits Ectopic Calcification in Various Pseudoxanthoma Elasticum and
Miguel D Ferrer1,2,3,4, Maria Del Mar Pérez-Ferrer1,2,3, Marc Blasco1,2,3
1Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain.
Abstract:
Background/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6 zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6 mice were administered subcutaneously with CSL525 at 15 mg/kg thrice weekly for eight weeks. Vehicle-treated WT (C57BL/6J) and abcc6 mice served as controls, and muzzle skin calcification was quantified. In a third study, calcinosis cutis was induced in rats through subcutaneous administration of 0.15 mg FeCl3 at two sites in the thorax. Rats were administered either subcutaneous CSL525 (60 mg/kg) or vehicle (0.9% NaCl), and calcium content was measured in the skin. Results: CSL525 significantly reduced the calcified area (~40%) in abcc6a zebrafish larvae. The abcc6 mice receiving CSL525 showed a 57% inhibition of muzzle calcification compared to vehicle-treated abcc6 mice. CSL525 inhibited skin calcification development by 60% in the calcinosis cutis rat model. Conclusions: CSL525 may prove beneficial not only in preventing the progression of cardiovascular calcification but also in treating other ectopic calcification conditions, including skin calcification associated with genetic disorders such as PXE.
Insights
Hexasodium fytate (CSL525) effectively treats ectopic calcification in animal models. This crystallization inhibitor shows promise for conditions like pseudoxanthoma elasticum and calcinosis cutis.
Area of Science:
- Pharmacology
- Biochemistry
- Pathology
Background:
- Ectopic calcification involves pathological soft tissue mineralization.
- Hexasodium fytate (CSL525) is an investigational crystallization inhibitor.
- CSL525 targets ectopic calcification-related disorders.
Purpose of the Study:
- To evaluate CSL525 for treating soft tissue calcification.
- To assess CSL525 in animal models of pseudoxanthoma elasticum and calcinosis cutis.
Main Methods:
- Zebrafish (abcc6) larvae treated with CSL525 to quantify spinal mineralization.
- Abcc6 mice treated with CSL525 to assess muzzle skin calcification.
- Rats with induced calcinosis cutis treated with CSL525 to measure skin calcium content.
Main Results:
- CSL525 reduced spinal calcification in zebrafish by approximately 40%.
- CSL525 inhibited muzzle calcification in abcc6 mice by 57%.
- CSL525 reduced skin calcification in rats by 60%.
Conclusions:
- CSL525 demonstrates efficacy in reducing ectopic calcification across multiple animal models.
- CSL525 may offer therapeutic benefits for cardiovascular and skin calcification.
- CSL525 shows potential for treating genetic disorders like pseudoxanthoma elasticum.
