How is Parkinson’s Disease Best Treated? A Comparative Analysis of CRISPR-Cas9 and iPSC-Based Gene Therapies

Parkinson's disease (PD) is a devastating neurological condition with little long-term treatment options. Gene therapy has emerged as a potential way to address the underlying pathology of the disease entirely. This paper has examined two main gene therapy approaches: direct in vivo gene editing with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9, and cell replacement therapy with induced pluripotent stem cells (iPSCs). The paper considers the mechanisms of action, therapeutic potential, and overall challenges and barriers to implementation for each approach. The analysis found that both CRISPR-Cas9 and iPSCs have potential as gene therapeutic approaches or modalities, with distinctions. CRISPR-Cas9 have the opportunity to correct the genetic cause of familial PD. However, there were large unresolved challenges about delivery and off-target safety. iPSCs therapy replaces the lost dopaminergic neurons and is a more generic approach, with challenges related to manufacturing the cells and clinical delivery, but these appear more tractable challenges and with more advanced methods available now. Overall, iPSCs based cell replacement therapy is a more preferable and promising short-to-medium term treatment option for a wider population of PD patients.