De Marchi Fabiola, Lombardi Ivan, Bombaci Alessandro, Diamanti Luca, Olivero Marco, Perciballi Elisa, Tornabene Danilo, Vulcano Edvige, Ferrari Daniela, Mazzini Letizia
Department of Neurology, Maggiore della Carità Hospital, University of Piemonte Orientale, Novara, Italy.
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.
Expert Rev Neurother. 2025 Jul;25(7):773-789. doi: 10.1080/14737175.2025.2508781. Epub 2025 May 21.
Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce. The emergence of regenerative medicine presents a new frontier for ALS treatment.
This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving focus to regenerative medicine. The article includes coverage of stem cell-based therapies, including mesenchymal, neural and induced pluripotent stem cells; all of which may offer potential neuroprotective and immunomodulatory effects. Gene therapy, particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, with tofersen becoming the first FDA-approved genetic therapy for ALS. The article also covers emerging approaches such as extracellular vesicles, immune-modulating therapies, and bioengineering techniques, including CRISPR-based gene editing and cellular reprogramming, that hold promise for altering disease progression.
While regenerative medicine provides hope for ALS patients, significant challenges remain. Biomarkers will play a crucial role in guiding personalized treatment strategies, ensuring targeted interventions. Future research should prioritize optimizing combinatory approaches, integrating different therapy strategies to maximize patient outcomes. Although regenerative medicine is still in its early clinical stages, its integration into ALS treatment paradigms could redefine disease management and alter its natural course.
尽管经过数十年的研究，但针对肌萎缩侧索硬化症（ALS）的有效疾病修饰疗法仍然稀缺。再生医学的出现为ALS治疗开辟了新的前沿领域。
本综述基于使用PubMed、Scopus和临床试验数据库对ALS近期治疗进展进行的全面文献检索，重点关注再生医学。文章涵盖了基于干细胞的疗法，包括间充质干细胞、神经干细胞和诱导多能干细胞；所有这些疗法都可能具有潜在的神经保护和免疫调节作用。基因疗法，特别是针对ALS相关突变的反义寡核苷酸，已受到关注，托法替布成为首个获得美国食品药品监督管理局（FDA）批准的用于ALS的基因疗法。文章还介绍了细胞外囊泡、免疫调节疗法和生物工程技术等新兴方法，包括基于CRISPR的基因编辑和细胞重编程，这些方法有望改变疾病进展。
虽然再生医学为ALS患者带来了希望，但仍存在重大挑战。生物标志物将在指导个性化治疗策略、确保靶向干预方面发挥关键作用。未来的研究应优先优化联合治疗方法，整合不同的治疗策略以最大化患者的治疗效果。尽管再生医学仍处于临床早期阶段，但将其纳入ALS治疗模式可能会重新定义疾病管理并改变其自然病程。
