Ferrer Miguel D, Pérez-Ferrer Maria Del Mar, Blasco Marc, Jacobs Ida Joely, Li Qiaoli, Vanakker Olivier M, Dangreau Lisa, López Andrea, Malagraba Gianluca, Bassissi Firas, Perelló Joan, Salcedo Carolina
Renal Lithiasis and Pathological Calcification Group (LiRCaP), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma, Spain.
Health Research Institute of the Balearic Islands (IdISBa), 07010 Palma, Spain.
Pharmaceuticals (Basel). 2025 Apr 14;18(4):567. doi: 10.3390/ph18040567.
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. In a first study, 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, mice were administered subcutaneously with CSL525 at 15 mg/kg thrice weekly for eight weeks. Vehicle-treated WT (C57BL/6J) and 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 FeCl 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. CSL525 significantly reduced the calcified area (~40%) in zebrafish larvae. The mice receiving CSL525 showed a 57% inhibition of muzzle calcification compared to vehicle-treated mice. CSL525 inhibited skin calcification development by 60% in the calcinosis cutis rat model. 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.
异位钙化是一种病理状态，其特征是由于磷酸钙晶体的沉积导致软组织矿化。植酸六钠（CSL525，以前称为SNF472）是一种正在开发用于治疗与异位钙化相关疾病的结晶抑制剂。我们的目的是在弹性假黄瘤和皮肤钙质沉着症的动物模型中研究CSL525对软组织钙化疾病的治疗作用。在第一项研究中，将斑马鱼幼虫暴露于1 mM CSL525中7天，或在无CSL525的相同条件下饲养，并对脊柱矿化进行定量。在第二项研究中，每周三次给小鼠皮下注射15 mg/kg的CSL525，持续八周。用载体处理的野生型（C57BL/6J）小鼠作为对照，并对口鼻部皮肤钙化进行定量。在第三项研究中，通过在大鼠胸部的两个部位皮下注射0.15 mg氯化铁诱导皮肤钙质沉着症。给大鼠皮下注射CSL525（60 mg/kg）或载体（0.9%氯化钠），并测量皮肤中的钙含量。CSL525显著减少了斑马鱼幼虫的钙化面积（约40%）。与用载体处理的小鼠相比，接受CSL525的小鼠口鼻部钙化受到57%的抑制。在皮肤钙质沉着症大鼠模型中，CSL525抑制皮肤钙化发展达60%。CSL525可能不仅在预防心血管钙化进展方面有益，而且在治疗其他异位钙化病症方面也有益，包括与诸如弹性假黄瘤等遗传疾病相关的皮肤钙化。
