Neurons Under Genetic Control: What Are the Next Steps Towards the Treatment of Movement Disorders?

Since the implementation of deep-brain stimulation as a therapy for movement disorders, there has been little progress in the clinical application of novel alternative treatments. Movement disorders are a group of neurological conditions, which are characterised with impairment of voluntary movement and share similar anatomical loci across the basal ganglia. The focus of the current review is on Parkinson's disease and Huntington's disease as they are the most investigated hypokinetic and hyperkinetic movement disorders, respectively. The last decade has seen enormous advances in the development of laboratory techniques that control neuronal activity. The two major ways to genetically control the neuronal function are: 1) expression of light-sensitive proteins that allow for the optogenetic control of the neuronal spiking and 2) expression or suppression of genes that control the transcription and translation of proteins. However, the translation of these methodologies from the laboratories into the clinics still faces significant challenges. The article summarizes the latest developments in optogenetics and gene therapy. Here, I compare the physiological mechanisms of established electrical deep brain stimulation to the experimental optogenetical deep brain stimulation. I compare also the advantages of DNA- and RNA-based techniques for gene therapy of familial movement disorders. I highlight the benefits and the major issues of each technique and I discuss the translational potential and clinical feasibility of optogenetic stimulation and gene expression control. The review emphasises recent technical breakthroughs that could initiate a notable leap in the treatment of movement disorders.