CRISPR and Myelin regeneration: a systematic review of applications in demyelinating CNS Disorders, with a focus on MS.

Aims: Current treatments for demyelinating disorders focus on slowing progression but fail to repair damaged myelin. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -based technology has the potential to address key challenges in myelin repair by targeting genetic dysfunctions, modulating immune responses, and promoting oligodendrocyte differentiation. This systematic review aimed to evaluate CRISPR applications for myelin regeneration.

Methods: A comprehensive search of PubMed, Scopus, and other databases identified 48 studies. The included studies employed CRISPR in diverse experimental models, targeting genes associated with immune regulation and astrocyte activity, as well as correcting RNA splicing dysfunctions linked to neurodegeneration.

Results: CRISPR-edited stem cells showed significant potential in promoting myelin regeneration, with enhanced functional recovery in animal models of multiple sclerosis (MS). While most research focused on MS, promising applications were also observed in neuromyelitis optica spectrum disorder (NMOSD), such as reducing astrocytic damage via AQP4 targeting, and in progressive multifocal leukoencephalopathy (PML), where CRISPR disrupted JC polyomavirus replication.

Conclusions: Despite its promise, challenges remain. Future research should prioritize optimizing CRISPR delivery systems, expanding applications to underexplored disorders, and conducting long-term safety assessments. Early results are encouraging, but further studies are essential to translate preclinical success into clinical therapies.