Title : Efficacy of gene therapy for attenuating and reversing neuronal damage in Parkinson’s disease: A narrative-based bibliometric review
Abstract:
Parkinson’s disease (PD) is a progressive neurodegenerative disorder defined by the selective loss of dopaminergic neurons in the substantia nigra, resulting in both motor dysfunction and a range of non-motor symptoms. Although current pharmacologic and surgical interventions provide symptomatic relief, they do not address the underlying neurodegenerative processes driving disease progression. Advances in the understanding of PD pathophysiology, especially through the identification of monogenic forms of the disease, reveals key mechanisms such as impaired proteostasis and chronic neuroinflammation, which have made gene therapy a promising disease-modifying strategy capable of delivering sustained therapeutic effects through targeted molecular intervention in affected neural circuits.
This narrative-based and bibliometric review synthesizes findings from the 100 most peer-reviewed studies with the keywords "Parkinson's disease," "gene therapy," and "neuronal damage recovery" in the Web of Science database to evaluate the efficacy of gene therapy in attenuating, and potentially reversing, neuronal damage in PD. Studies were selected based on methodological rigor and relevance to disease-modifying outcomes, with those lacking clear experimental or clinical frameworks excluded. The author and institutional metadata was analyzed using RStudio’s bibliometrix package by mapping frequencies and co-authorship relations, while narrative synthesis was conducted using structured thematic mapping and extracting qualitative information from each article via a standardized form. Clinical investigations assessed therapeutic impact using validated measures such as the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), alongside neuroimaging markers of dopaminergic function.
Preclinical studies employed in vitro systems and animal models to examine molecular and cellular mechanisms, with a special attention to pathways involving PINK1 and Parkin-mediated mitochondrial quality control via oxidative stress and α-synuclein aggregation. Gene therapy strategies analyzed included viral vector–mediated delivery systems, such as adeno-associated viruses, and the administration of neurotrophic factors including glial cell line-derived neurotrophic factor (GDNF). In parallel, genetic association studies, including genome-wide association studies (GWAS), were considered to contextualize therapeutic targets within broader disease susceptibility frameworks. The general consensus of the literature is that gene therapy approaches consistently demonstrated the capacity to enhance neuronal survival by improving dopaminergic signaling in preclinical models. Clinical studies reported modest but measurable improvements in motor function and disease progression metrics, the effects being most exaggerated in early-stage patients receiving targeted interventions.
On the other hand, bibliometric trends indicate a growing research emphasis on PD within the broader neurodegenerative field accompanied by increased prioritization of disease-modifying therapies and precision medicine approaches. Analysis of highly cited neurodegenerative research revealed that 27% of publications focused on PD, exceeding Alzheimer’s disease (17%), indicating strong research emphasis. Highly cited studies focused on recent advances in diagnostic accuracy and the importance of oxidative stress across numerous neurodegenerative diseases.
Collectively, the evidence suggests that gene therapy holds substantial promise in slowing the progression of neuronal damage in Parkinson’s disease, with stronger support for neuroprotective effects than the reversal of advanced neurodegeneration. However, clinical translation remains constrained by challenges related to targeted delivery and long-term safety. Continued advances in vector design and early diagnostic capabilities will be critical in determining the ultimate impact of gene therapy in PD management.
