Gene therapy as a viable therapeutic approach for Parkinson's disease

Abstract

Parkinson’s Disease (PD) is a neurological disorder affecting the basal ganglia in which the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) manifests as a complex array of motor and non-motor symptoms. Due to the lack of treatment for preventing the neurodegenerative process of PD, the only available therapy options involve managing the clinical symptoms resulting from dopamine (DA) depletion in the basal ganglia. The most widely implemented treatment is the pharmacological agent L-DOPA which serves as the precursor to dopamine. Although L-DOPA administration is initially effective in improving motor function and patient life quality, its therapeutic effect diminishes as PD pathology progressively worsens over time and side effects such as L-DOPA induced dyskinesia become apparent. Researchers are now seeking to alleviate the symptoms of PD on a molecular basis with gene therapy in which the three therapeutic strategies target specific genes involved in either increasing dopamine production, regulating the pathways of the basal ganglia, or protecting dopaminergic neurons of the nigrostriatal pathway. Current research is focused on investigating the efficacy and overall safety of gene therapy through delivery of the genes responsible for aromatic L-acid decarboxylase (AADC), glutamic acid decarboxylase (GAD), glial cell derived neurotrophic factor (GDNF), and neurturin (NRTN). Although these methods of gene therapy are relatively new and still developing, they present a promising direction for PD treatment. In this review, the various gene therapy strategies designed for improving parkinsonism are evaluated for safety and efficacy.