Bangolo Ayrton, Amoozgar Behzad, Zhang Lili, Gill Sarvarinder, Lushimba Milolo Daniel, Ngindu Kankonde Justin, Mbuyi Batakamuna Claude, Tassan Robert, Cho Christina, Bukasa-Kakamba John, Mowatt-Pesce Kelley
Department of Hematology and Oncology, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601, USA.
Department of Internal Medicine, Université Notre-Dame du Kasayi, Kananga P.O. Box 70, Democratic Republic of the Congo.
Biomedicines. 2025 Aug 19;13(8):2022. doi: 10.3390/biomedicines13082022.
Hemophilias and hemoglobinopathies-including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia-are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide.
血友病和血红蛋白病，包括甲型和乙型血友病、镰状细胞病（SCD）和β地中海贫血，是使人衰弱的遗传性疾病，给全球健康带来重大负担。虽然传统治疗以因子替代和输血为中心，但这些方法仍然是姑息性的，在许多地区的可及性和持久性有限。基于免疫的疗法（如依美珠单抗、康西珠单抗、克唑单抗）、病毒载体介导的基因添加（如Roctavian、Hemgenix）以及基因修饰的自体干细胞疗法（如Zynteglo、Casgevy）的最新进展开创了疾病修饰和潜在治愈性干预的新时代。这些疗法具有持久的疗效并能改善生活质量，尤其是在成年人群中。然而，由于成本高昂、基础设施有限和监管异质性，全球卫生系统的实施情况仍然参差不齐。此外，诸如长期监测、弱势群体的知情同意以及基因改造的社会认知等伦理考量也带来了持续的挑战。多重基因组编辑、免疫逃避供体平台、合成生物学和人工智能驱动的治疗建模等创新有望拓展治疗前景。公平获取，特别是在疾病负担最重的地区，将需要合作性的资助策略、区域能力建设和包容性的监管框架。本综述总结了当前治愈性疗法的现状，概述了实施障碍，并呼吁采取协调一致的国际行动，以确保变革性治疗惠及全球所有受影响的个体。
