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基于抗体和适配体的骨关节炎治疗方法:抗体的应用及适配体的前景。

Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.

作者信息

Chen Huaizhi, Ye Zijian, Korpershoek Jasmijn V, Creemers Laura B, Weinans Harrie, Rios Jaqueline Lourdes

机构信息

Department of Orthopedic Surgery, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.

Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Mol Ther Nucleic Acids. 2025 May 5;36(2):102552. doi: 10.1016/j.omtn.2025.102552. eCollection 2025 Jun 10.

Abstract

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients' quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducing inflammation and pain in the joint targeting specific molecular key players, instead of a systemic and generalized approach like with non-steroidal anti-inflammatory drugs. Aptamers' properties, including structure versatility, reduced immunogenicity, and flexible administration methods, position them as high-potential candidates for OA treatment. This review summarizes results from clinical trials applying monoclonal antibodies to treat OA, preclinical research, and the development of aptamers as a new generation of targeting agents. Meanwhile, it provides a comprehensive comparison of the characteristics, advantages, and limitations of aptamers versus monoclonal antibodies. Notably, the promising applications of aptamers, demonstrated in other inflammatory and degenerative conditions, underscore their potential for OA therapy. We anticipate that the application of aptamer could offer a new way of OA pharmacological intervention.

摘要

骨关节炎(OA)是一种常见的退行性炎症性关节疾病,其关节软骨会逐渐丧失,这会损害患者的生活质量。尽管已经进行了大量研究来阐明骨关节炎的发病机制,但目前尚无经监管部门批准的、能改变病情的骨关节炎药物。到目前为止,骨关节炎的药物治疗主要集中在对炎症和疼痛的全身性抑制。目前,单克隆抗体和核酸适配体作为靶向治疗方法出现,它们通过应对骨关节炎带来的复杂挑战,提供了潜在的替代方案,比如针对特定分子关键靶点特异性减轻关节炎症和疼痛,而不是像使用非甾体抗炎药那样采用全身性和普遍性的方法。适配体的特性,包括结构多样性、免疫原性降低以及给药方式灵活,使其成为骨关节炎治疗的高潜力候选药物。这篇综述总结了应用单克隆抗体治疗骨关节炎的临床试验结果、临床前研究以及作为新一代靶向药物的适配体的研发情况。同时,它对适配体与单克隆抗体的特性、优势和局限性进行了全面比较。值得注意的是,适配体在其他炎症和退行性疾病中已展现出的有前景的应用,突出了它们在骨关节炎治疗中的潜力。我们预计适配体的应用可为骨关节炎的药物干预提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/12145836/5f66b7068448/fx1.jpg

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