Department of Pathology, Stanford University School of Medicine, Palo Alto, California, USA.
Department of Pathology, Washington University, St Louis, Missouri, USA.
Vox Sang. 2024 Jun;119(6):521-528. doi: 10.1111/vox.13612. Epub 2024 Mar 15.
Sickle cell disease (SCD) is a type of hemoglobinopathy due to an autosomal recessive genetic defect, causing significant red cell sickling, multi-organ damage and long-term severe morbidities. Due to its complicated care and the impact on quality of life, a curative treatment for SCD is highly desirable. In recent years, gene therapy is emerging as a curative option for SCD, where autologous haematopoietic stem cells are collected from SCD patients and genetically modified ex vivo to reduce its sickling tendency before reinfusion. Although still largely investigational, a limited number of gene therapy options have been recently granted approval for SCD patients. Published data are still currently limited, but early studies have so far demonstrated the intended outcomes of less vaso-occlusive crisis and haemolysis. Nonetheless, despite its curative potential, larger clinical trials and longer follow-up period are still necessary to evaluate the safety of this treatment option, especially the risk of unintended genetic modifications. Furthermore, SCD patients frequently have limited access to specialty care; hence, the issues of affordability and accessibility to SCD gene therapy must also be addressed for it to benefit the appropriate patient population.
镰状细胞病（SCD）是一种由于常染色体隐性遗传缺陷引起的血红蛋白病，导致显著的红细胞镰变、多器官损伤和长期严重的病态。由于其护理复杂且对生活质量有影响，因此非常需要一种治疗 SCD 的方法。近年来，基因治疗作为 SCD 的一种有前途的治疗方法，从 SCD 患者中采集自体造血干细胞，并在体外进行基因修饰，以降低再输注前的镰变倾向。尽管仍在很大程度上处于研究阶段，但最近已有少数基因治疗方法获得 SCD 患者的批准。已发表的数据仍然有限，但早期研究迄今为止已证明了较少的血管阻塞性危象和溶血的预期结果。然而，尽管具有潜在的治疗效果，但仍需要更大规模的临床试验和更长的随访期来评估这种治疗方法的安全性，尤其是意外基因修饰的风险。此外，SCD 患者通常难以获得专科护理；因此，必须解决 SCD 基因治疗的可负担性和可及性问题，以便使适当的患者群体受益。
