A Review of Gene Therapy for Parkinson's Disease to Control Dopaminergic Neurons

Authors: Rajesham VV , Rachana Y and Rama Rao T

DOI: 10.23880/nnoaj-16000194

Volume 10, Issue 1

Abstract

Parkinson's disease (PD) is the most common neurodegenerative disorder after Alzheimer's disease. Both motor and nonmotor symptoms are caused by the gradual death of dopaminergic neurones in the substantia nigra and a reduction in dopamine (DA) levels. Early-phase clinical trials have shown that DA replacement gene treatments that raise DA transmitter levels, such as Adeno-associated virus (AAV)–glutamic acid decarboxylase (GAD) and L-amino acid decarboxylase (AADC) gene therapies, are safe and effective. Strategies for disease modification, which try to reduce the course of the disease, seem to be effective. These include treatments that target neurotrophic factors, downstream pathways, and midbrain dopaminergic neuronal factors, all of which have demonstrated promise in preclinical and clinical studies. Other possible gene treatments that target both glial cells and dopaminergic neurones may have similar results, but further study is required. The potential of neurotrophic factors, including Neurturin, Glial-cell-line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), to promote dopaminergic neurone survival is also being studied. Furthermore, intriguing approaches include gene treatments that target important downstream processes such endoplasmic reticulum (ER) stress, mitochondrial function, and the autophagy–lysosome pathway. As gene editing and delivery methods advance, new avenues for creating potent gene treatments for Parkinson's disease become available. A possible treatment for Parkinson's disease appears to be the CRISPR-Cas9 system, a ground-breaking technology developed in the past ten years that enables precise and instantaneous genome editing in almost any living species.

Keywords: Parkinson's Disease (PD); Gene Editing; Stress; Neurturin, Glial-Cell-Line-Derived Neurotrophic Factor (GDNF); Dopamine, Basal Ganglia, Α-Synuclein; Crispr-Cas9

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