儿童骨骼相关罕见病的基因治疗进展  

Advancements in gene therapy for pediatric rare diseases associated with skeletal conditions

作　　者：贲雨龙 刘朋 郑朋飞 Ben Yulong;Liu Peng;Zheng Pengfei(Department of Orthopaedics,Children's Hospital of Nanjing Medical University,Nanjing 210000,China;Jiangsu Ocean University,Lianyungang 222000,China)

机构地区：[1]南京医科大学附属儿童医院骨科,南京210000 [2]江苏海洋大学,连云港222000

出　　处：《中华骨科杂志》2024年第18期1246-1254,共9页Chinese Journal of Orthopaedics

摘　　要：罕见病又称为孤儿病,指患病率低、病类繁复且症状严重的一类疾病。罕见病大多起病早,常于儿童时期便开始出现症状,其中骨骼相关改变为其重要组成部分。这类罕见病常具有遗传性,缺乏有效的治疗手段。随着人类基因领域研究的进步和突破,许多罕见病的病因被逐渐揭露。本文综述儿童骨骼罕见病基因治疗领域的最新进展及其在儿童骨骼相关罕见疾病治疗中的应用。其中特别关注了成骨不全、X-连锁低血磷性抗维生素D佝偻病、软骨发育不良等罕见病,并介绍相关的基因治疗策略。成骨不全主要采用骨髓间质干细胞移植和基因编辑技术,已有实验数据证实其有效性和安全性;X-连锁低血磷性抗维生素D佝偻病则重点研究了FGF23单克隆抗体,临床试验显示该方法能显著改善患者症状;软骨发育不良主要采用小分子酪氨酸激酶抑制剂和C型钠尿肽类似物等,研究进展表明这些方法在改善骨骼生长方面效果显著。尽管目前基因治疗的研究仍处于早期阶段,但它为治疗这些罕见疾病提供了希望,并有望成为未来治疗儿童骨骼相关罕见病的手段之一。Rare diseases,also known as orphan diseases,refer to a category of illnesses characterized by low prevalence,complex disease profiles,and severe symptoms.Rare diseases often manifest early in life,with symptoms frequently appearing in childhood.Among these conditions,changes in bone structure play a crucial role,and many rare diseases of this nature have a genetic basis and lack effective treatment modalities.With advances and breakthroughs in human gene research,the etiology of many rare diseases has been gradually uncovered.This paper reviews recent advances in gene therapy for rare pediatric bone diseases and its application in treating skeletal-related rare conditions.Special attention is directed towards cases such as osteogenesis imperfecta,X-linked hypophosphatemia and achondroplasia,and related gene therapy strategies are introduced.Osteogenesis imperfecta is primarily treated with bone marrow-derived mesenchymal stem cell transplantation and gene editing techniques,with experimental data validating their efficacy and safety;X-linked hypophosphatemic rickets has focused on FGF23 monoclonal antibodies,with clinical trials showing significant improvement in patient symptoms.Achondroplasia is primarily treated with small molecule tyrosine kinase inhibitors and C-type natriuretic peptide analogs,with research indicating these methods significantly improve bone growth.Although gene therapy research is still in its early stages,it provides hope for treating these rare diseases and may become a viable future treatment option for pediatric skeletal-related rare conditions.

关 键 词：儿童 骨骼 少见病 基因治疗 

分 类 号：R726.8[医药卫生—儿科]