Gene Therapy for Parkinson’s Disease: Evaluating Current Platforms and Clinical Outcomes

Abstract

Parkinson’s disease management remains heavily reliant on symptomatic treatments, which often lead to debilitating complications over time, creating a pressing need for interventions that offer durable benefits and potentially modify disease progression. While gene therapy has emerged as a promising strategy to address this unmet need, its clinical translation has been marked by both encouraging advances and significant setbacks. This paper therefore aims to critically evaluate the current landscape of gene therapy for Parkinson’s disease, synthesizing evidence on its platforms, clinical outcomes, and persistent challenges. This paper comprehensively examines molecular strategies that extend beyond dopamine replacement, including enhanced dopamine synthesis, neurotrophic support, and neural circuit modulation. It analyzes the viral vector platforms that enable these therapies, with a focus on adeno-associated virus and lentivirus (LV) and underscores the critical role of convection-enhanced delivery for achieving adequate distribution in the human brain. Furthermore, the paper delves into the designs and endpoint challenges of pivotal clinical trials, synthesizes the available safety and immunogenicity data, and discusses the impact of surgical delivery precision on therapeutic efficacy. Looking forward, the future of gene therapy for Parkinson’s disease hinges on overcoming key hurdles in vector design, immune response modulation, and biomarker development. Success will depend on refining delivery techniques to ensure consistent target coverage and designing trials capable of definitively demonstrating disease-modifying effects. As these innovative platforms continue to evolve, they hold the potential to fundamentally transform the therapeutic paradigm for Parkinson’s disease, moving from symptomatic management to long-term disease modification.