INTRODUCTION: Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce, with riluzole and edaravone offering only limited benefits. The emergence of regenerative medicine, including stem cell therapy, gene-based interventions, and bioengineering strategies, presents a new frontier for ALS treatment. AREAS COVERED: This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving particular focus to regenerative medicine. The article includes coverage of stem cell-based therapies, including mesenchymal stem cells, neural stem cells, 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. EXPERT OPINION: While regenerative medicine provides hope for ALS patients, significant challenges remain. Biomarkers will play a crucial role in guiding personalized treatment strategies, ensuring targeted and effective 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 potentially alter its natural course.