Nielsen Jeffery J, Low Stewart A, Chen Christopher, Li Xinlan, Mbachu Ephraim, Trigg Lina, Sun Siyuan, Tremby Madeline, Hadap Rahul, Low Philip S
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Novosteo Inc., West Lafayette, IN 47906, USA.
Biomedicines. 2024 Mar 8;12(3):612. doi: 10.3390/biomedicines12030612.
Spinal fusions are performed to treat congenital skeletal malformations, spondylosis, degenerative disk diseases, and other pathologies of the vertebrae that can be resolved by reducing motion between neighboring vertebrae. Unfortunately, up to 100,000 fusion procedures fail per year in the United States, suggesting that efforts to develop new approaches to improve spinal fusions are justified. We have explored whether the use of an osteotropic oligopeptide to target an attached bone anabolic agent to the fusion site might be exploited to both accelerate the mineralization process and improve the overall success rate of spinal fusions. The data presented below demonstrate that subcutaneous administration of a modified abaloparatide conjugated to 20 mer of D-glutamic acid not only localizes at the spinal fusion site but also outperforms the standard of care (topically applied BMP2) in both speed of mineralization ( < 0.05) and overall fusion success rate ( < 0.05) in a posterior lateral spinal fusion model in male and female rats, with no accompanying ectopic mineralization. Because the bone-localizing conjugate can be administered ad libitum post-surgery, and since the procedure appears to improve on standard of care, we conclude that administration of a bone-homing anabolic agent for improvement of spinal fusion surgeries warrants further exploration.
脊柱融合术用于治疗先天性骨骼畸形、脊椎关节强硬、椎间盘退行性疾病以及其他可通过减少相邻椎体间活动来解决的脊椎病变。不幸的是，在美国每年多达10万例融合手术失败，这表明研发改善脊柱融合术新方法的努力是合理的。我们探讨了使用亲骨性寡肽将附着的骨合成代谢剂靶向至融合部位，是否可用于加速矿化过程并提高脊柱融合术的总体成功率。以下数据表明，皮下注射与20聚体D-谷氨酸偶联的改良阿巴洛肽，不仅定位于脊柱融合部位，而且在雄性和雌性大鼠的后外侧脊柱融合模型中，在矿化速度（<0.05）和总体融合成功率（<0.05）方面均优于标准治疗方法（局部应用BMP2），且无伴随的异位矿化。由于骨定位偶联物可在手术后随意给药，并且该方法似乎优于标准治疗方法，我们得出结论，给予骨归巢合成代谢剂以改善脊柱融合手术值得进一步探索。
