Gene therapy treatment for Parkinson’s disease

Abstract: Parkinson’s disease (PD) is the most common neurodegenerative disorder after Alzheimer’s disease and today more than 6 million people are living with PD world-wide (2018). PD is characterized by muscle stiffness, shaking at rest, and postural imbalance. The symptoms are caused by a decreased dopamine (DA) level in the brain due to a gradual loss of DA producing neurons. The cause and trigger of the disease is unknown but is believed to be a combination of both environmental and genetic factors. No treatment that can cure or slow down the disease progression is available; there are on the other hand treatments for symptom relief. Gene therapy is one potential treatment option for symptoms relief in PD. In gene therapy, genetic material is introduced into cells in the brain using viral vectors with the goal of restoring DA production. In this study gene material for two important enzymes in the dopamine production has been injected into the brain of rats using viral vectors. The two enzymes are Tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1). A destabilization domain was added to regulate the activity of the enzymes. All proteins coupled to the domain are degraded in the absence of trimethoprim (TMP), thus enabling regulation and fine tuning of the enzyme activity in the brain. The dopamine and serotonin in the brain, as well as their precursors and metabolites were monitored using HPLC-ECD. The result showed a restored production in the non-regulated group and the GCH1 regulated group but not in the TH regulated ones. The TMP concentration in brain was monitored using HPLC-MS and found to be lower than expected. Further studies have to be done in order to optimize the conditions and fine tuning the regulation of the constructs.