Gene-Based Therapeutics for Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a complex multifactorial disorder that is not yet fully surmised, and it is only when such a disease is tackled on multiple levels simultaneously that we should expect to see fruitful results. Gene therapy is a modern medical practice that theoretically and, so far, practically, has demonstrated its capability in joining the battle against PD and other complex disorders on most if not all fronts. This review discusses how gene therapy can efficiently replace current forms of therapy such as drugs, personalized medicine or invasive surgery. Furthermore, we discuss the importance of enhancing delivery techniques to increase the level of transduction and control of gene expression or tissue specificity. Importantly, the results of current trials establish the safety, efficacy and applicability of gene therapy for PD. Gene therapy’s variety of potential in interfering with PD’s pathology by improving basal ganglial circuitry, enhancing dopamine synthesis, delivering neuroprotection or preventing neurodegeneration may one day achieve symptomatic benefit, disease modification and eradication.

Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies

“…In animal models of PD, glutamic acid decarboxylase (GAD) gene transfer and other approaches that modify GABA synthesis in the subthalamic nucleus enhance basal ganglia function ( Muñoz et al, 2020 ). Gene therapy might be a viable treatment option, which involves inserting the glutamic acid decarboxylase gene (GAD) into the subthalamic nucleus ( Shalaby and El-Agnaf, 2022 ). GAD is the rate-limiting enzyme for GABA synthesis, and PD affects the function of both GABA efferents to the subthalamic nucleus and their targets within the basal ganglia circuitry ( Stoddard-Bennett and Reijo Pera, 2019 ; Muñoz et al, 2020 ).…”

Preparation of Chitosan Nanoparticles through a Readily Solvent-Exchange Process for Efficient and Enhanced Gene Delivery

“…Since the first clinical trial for the treatment of Gaucher disease in 1988, gene therapy has expanded its application for the treatment of genetic diseases, tumors, respiratory diseases, cardiovascular and cerebrovascular diseases, digestive diseases, blood system diseases, autoimmune diseases, endocrine system diseases, central nervous system diseases, and so on. − Especially with the discovery of the CRISPR-Cas9 system, gene therapy as a therapeutic strategy shows great potential . Gene therapy has advantages over traditional drugs, such as overcoming chemical drug resistance and the inability to correct genetic defects .…”