Gene-based Therapies in Parkinson's Disease

Abstract

Parkinson's disease (PD) is a progressive neurological disorder characterized primarily by the degeneration of nigrostriatal dopaminergic neurons and diminution of the neurotransmitter dopamine. Though dopamine replacement therapies such as levodopa can improve the symptoms of PD, the benefits may be overshadowed by side effects and the onset of symptoms not responsive to dopaminergic treatments (e.g., autonomic symptoms, gait and balance problems, and cognitive impairment). Furthermore, no therapies have proven to slow the neurodegenerative process. Novel approaches to address these difficult problems, and others, are being sought. Over the last decade, several innovative gene therapies for PD have entered human clinical trials in an effort to address both symptomatic and potential disease-modifying effects. Though the results of these trials have been mixed, the therapies have generally been safe and well-tolerated, suggesting gene therapy may be a viable treatment for PD in the future. This article will review past and current clinical trials of gene therapies for PD. In addition, novel preclinical approaches to gene therapy for PD will be described.

Therapy for Parkinson's Disease: What is in the Pipeline?

“…An alternative approach to restorative treatment is represented by the viral vector-based targeted delivery of therapeutic genes. This approach is covered in elsewhere in this journal [71].…”

Inhibition by Multifunctional Magnetic Nanoparticles Loaded with Alpha-Synuclein RNAi Plasmid in a Parkinson's Disease Model

“…Over the previous decade, several innovative gene therapies for PD have been shown to be relatively safe and well-tolerated, suggesting that gene therapy may be a viable treatment option for PD in the future 10. RNA interference (RNAi) is one method that can be used to reduce SNCA gene expression.…”

CRISPR-Cas9: a new and promising player in gene therapy

“…The strategies of gene therapy are diverse, such as rectifying, replacing or deleting the culprit genes in genetic diseases, producing disabling mutations in pathogen genomes to combat infectious diseases or inducing therapeutic or protective somatic mutations. It is a promising therapy for a wide range of human diseases including hematological diseases,1 2 cancer,3 AIDS,4 diabetes,5 6 heart failure,7 and neurodegenerative diseases 8. Up to now, there has been more than 2000 gene therapy clinical trials worldwide,9 with a few gene therapy products having already been approved by authorities, such as Gendicine for head and neck squamous cell carcinoma in China, and Cerepro for malignant brain tumours in Europe 10…”