Biophysics and Beyond

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor and non-motor symptoms. Recent advances in cell replacement techniques have offered significant opportunities for restoring dopaminergic function. The combination of CRISPR-Cas9 genome editing with stem cell technology has emerged as a promising approach for treating both the genetic and cellular components of PD. This method allows the correction of disease-related mutations in patient-derived induced pluripotent stem cells (iPSCs), enabling their differentiation into dopaminergic neurons suitable for transplantation. These techniques can produce genetically corrected, functionally uniform cell populations, thereby enhancing the safety and efficacy of cell-based therapies. iPSC technology has led to renewed interest in stem cell therapy for PD, culminating in the first clinical trial utilizing iPSC-derived dopaminergic neurons in 2018. This review discusses the use of CRISPR-Cas9 for PD modeling and emphasizes its therapeutic potential when integrated with stem cell-based approaches. Furthermore, it examines the wide range of PD symptoms that could be addressed using advanced cell replacement methods with neurons produced from human pluripotent stem cells.