Abstract：
Intervertebral disc (IVD) degeneration (IVDD) is a leading cause of chronic low back pain. There is a strong clinical demand for more effective treatments for IVDD as conventional treatments provide only symptomatic relief rather than arresting IVDD progression. This study shows that senolytic therapy with local drug delivery can inhibit IVDD and restore IVD integrity. ABT263, a senolytic drug, is loaded in poly(lactic-co-glycolic acid) nanoparticles (PLGA-ABT) and intradiscally administered into injury-induced IVDD rat models. The single intradiscal injection of PLGA-ABT may enable local delivery of the drug to avascular IVD, prevention of potential systemic toxicity caused by systemic administration of senolytic drug, and morbidity caused by repetitive injections of free drug into the IVD. The strategy results in the selective elimination of senescent cells from the degenerative IVD, reduces expressions of pro-inflammatory cytokines and matrix proteases in the IVD, inhibits progression of IVDD, and even restores the IVD structure. This study demonstrates for the first time that local delivery of senolytic drug can effectively treat senescence-associated IVDD. This approach can be extended to treat other types of senescence-associated degenerative diseases.
摘要：
椎间盘（IVD）变性（IVDD）是慢性腰背痛的主要原因。对于IVDD的更有效治疗存在强烈的临床需求,因为常规治疗仅提供症状缓解而不是阻止IVDD进展。这项研究表明，局部给药的抗衰老疗法可以抑制IVDD并恢复IVD完整性。ABT263是一种抗衰老药物,负载在聚（乳酸-共-乙醇酸）纳米颗粒（PLGA-ABT）中，并向损伤诱导的IVDD大鼠模型中施用。PLGA-ABT的单次椎间盘内注射可以使药物局部递送至无血管IVD,预防由全身施用抗衰老药物引起的潜在全身毒性，以及由向IVD重复注射游离药物引起的发病率。该策略导致从退行性IVD中选择性消除衰老细胞，降低IVD中促炎细胞因子和基质蛋白酶的表达，抑制IVDD的进展，甚至恢复IVD结构。这项研究首次证明局部递送抗衰老药物可以有效治疗衰老相关的IVDD。这种方法可以扩展到治疗其他类型的衰老相关的退行性疾病。
