Gene therapy in Parkinson's disease consists of the creation of new cells that produce a specific neurotransmitter (dopamine), protect the neural system, or the modification of genes that are related to the disease. Then these cells are transplanted to a patient with the disease. There are different kinds of treatments that focus on reducing the symptoms of the disease but currently there is no cure.
Current treatments
Parkinson's disease (PD) is a progressive neurological disorder resulting from the death of cells in the substantia nigra that contain and produce dopamine. People with PD may develop disturbance in their motor activities. Some activities can be tremor or shaking, rigidity and slow movements (bradykinesia). Patients may eventually present certain psychiatric problems like depression and dementia. Current pharmacological intervention consist on the administration of L-dopa, a dopamine precursor. The L-dopa therapy increases dopamine production of the remaining nigral neurons. Other therapy is the deep brain electrical stimulation to modulate the overactivity of the subthalamic nucleus to the loss of dopamine signaling in the stratum. However, with this treatment, the number of substantia nigra neurons decrease so it becomes less efficient.
These treatments try to reduce the symptoms of the patient focusing on increasing the production of dopamine but they do not cure the disease. The new treatments for PD are in clinical trials and most of them are centered on gene therapy. With this, researchers expect to compensate the loss of dopamine or to protect the dopamine neurons from degeneration. The pharmacological and surgical therapies for PD focus on compensating the ganglia dysfunction caused by the degeneration of the dopaminergic neuron from substantia nigra.
Gene therapy background
There are many new PD treatments in clinical trials and several of those are focusing on gene therapeutic approaches that compensate the loss of dopamine or protect the nervous system dopamine neurons from degeneration. There are some important reasons for focusing on gene therapy as a treatment for PD. First of all, currently there is no cure for this disease. Secondly, some genes have been identified which can modulate the neuron phenotype or act as neuroprotective agents. Also, the environment of the brain cannot afford repeated injections into the region where the substantia nigra meets the striatum, the nigrostriatum. Therefore, gene therapy could be a single treatment appealing, viral vectors used in the therapy are diffusible and capable to do transduction of the striatum.
Gene therapy bases
The main idea of the gene therapy is to create new generations of cells that produce particular neurotransmitter (dopamine) and then transplant these cells to the patients with PD. This is because the neurons cannot proliferate nor be renewed; and replacing lost neurons it is a process that is currently going under investigation. Also, the use of embryonic dopaminergic cells cannot be used because these cells are difficult to obtain and modifications of cell can only be made on somatic cells, not germline. With the modifications of the transplanted cell, there can be a change in the expression of the genes or normalize them.
Types of gene therapy
There are several types of gene therapy. There are therapies for symptomatic approaches like the production of ectopic L-dopa, the full ectopic dopamine synthesis, the ectopic L-dopa conversion or the use of glutamic acid descarboxylase (GAD). Also there are disease modifying therapies like NTN or GNDF (glial cell line-derived neurotrophic factor), the regulation of the α-synuclein and Parkin gene expression. Currently the main studies are using AAV2 as a vector platform, making it the standard vector for this disease although a lentevirus has also been used. In the different types of the gene therapy, the investigations are encoding enzymes that are necessary for dopamine synthesis, such as tyrosine hydroxylase, GTP cyclohydrolase 1 and AADC.