Hexasodium Fytate (SNF472 or CSL525) Inhibits Ectopic Calcification in Various Pseudoxanthoma Elasticum and Calcinosis Cutis Animal Models

<b>Background/Objectives:</b> 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. <b>Methods:</b> In a first study, <i>abcc6^-/-</i> 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, <i>abcc6^-/-</i> mice were administered subcutaneously with CSL525 at 15 mg/kg thrice weekly for eight weeks. Vehicle-treated WT (C57BL/6J) and <i>abcc6^-/-</i> 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. <b>Results:</b> CSL525 significantly reduced the calcified area (~40%) in <i>abcc6a^-/-</i> zebrafish larvae. The <i>abcc6^-/-</i> mice receiving CSL525 showed a 57% inhibition of muzzle calcification compared to vehicle-treated <i>abcc6^-/-</i> mice. CSL525 inhibited skin calcification development by 60% in the calcinosis cutis rat model. <b>Conclusions:</b> 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.