From Dish to Disease: Human organoid models for advancing gene therapy in neurodegenerative disorders

Neurodegenerative diseases (NDDs) represent a profound challenge to global health, characterized by progressive neuronal dysfunction and loss, leading to debilitating conditions with limited therapeutic options. The complexity of human brain architecture and disease heterogeneity has historically hampered drug discovery, often due to the reliance on animal models that fail to fully recapitulate human disease pathology. The advent of induced pluripotent stem cell (iPSC) technology and subsequent development of three-dimensional (3D) organoid cultures have revolutionized disease modeling. These human-relevant models offer an unprecedented opportunity to study disease mechanisms and test novel interventions in a more physiologically accurate context. Concurrently, gene therapy strategies have emerged as promising avenues for targeted treatment, offering the potential to correct genetic defects or deliver therapeutic cargo directly to affected cells.This Research Topic aims to address the critical need for effective and translatable therapies for neurodegenerative diseases by exploring the synergistic potential of human organoid models and advanced gene therapy approaches. Despite significant progress in understanding NDDs, a substantial translational gap persists between preclinical findings and clinical success. We seek to highlight how iPSC-derived organoid cultures can serve as robust, patient-specific platforms to unravel complex disease pathologies, identify novel therapeutic targets, and, crucially, facilitate the preclinical evaluation of various gene therapy modalities. By bringing together cutting-edge research in both fields, this Topic endeavors to accelerate the development of precision medicine strategies, moving beyond traditional models to foster innovative solutions that translate more efficiently from the lab bench to improved patient outcomes.This Research Topic invites articles that showcase significant advancements in leveraging human organoid cultures for the development and testing of gene therapies targeting neurodegenerative diseases. We encourage submissions exploring the following themes:- Diverse Gene Therapy Approaches: AAV-based, CRISPR-Cas system-based gene editing, antisense oligonucleotide (ASO) therapy, siRNA, microRNA, or other RNA-based therapeutic strategies.- Broad Spectrum of Neurodegenerative Diseases: Including age-associated conditions such as Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease, as well as pediatric neurodegenerative diseases like Ataxia-telangiectasia, Hereditary Spastic Paraplegia (HSP), Wilson's disease, and Spinocerebellar Ataxia (SCA).- Design and Characterization of 3D Human Models: Development and in-depth characterization of patient-derived or iPSC-neuronal derived organoid models, detailing their ability to recapitulate disease-specific phenotypes and progression.- Preclinical Validation in Organoid Systems: Studies demonstrating the preclinical testing and efficacy evaluation of gene therapies within organoid-derived systems. Topic editors: Asmita Ghosh, Hemalatha Muralidharan, Yunpeng Cai Source: https://www.frontiersin.org/research-topics/76876/from-dish-to-disease-human-organoid-models-for-advancing-gene-therapy-in-neurodegenerative-disorders