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When it comes to battling neurological diseases, one of the most daunting is Parkinson’s Disease (PD). This debilitating condition is characterized by a slow and asymmetric onset of motor dysfunction in the form of muscle rigidity, impaired gait, hypokinesia, and tremor. PD motor symptoms are coupled with several non-motor symptoms, including disturbed mood, cognition, sleep patterns, and autonomic dysfunction such as heart rate changes, sweating, gastrointestinal problems, and difficulty swallowing.

Over time, the disease results in a loss of over half of the dopaminergic neurons in the substantia nigra pars compacta, a region within the hindbrain that controls movement and how your brain executes different cognitive functions. It is estimated that by the time patients exhibit motor symptoms associated with Parkinson’s, between 60% to 80% of dopamine neurons that project from the SNc throughout the brain have degenerated (Bernheimer et al., 1973; Marsden, 1990; Dauer & Przedborski, 2003). If Parkinson’s Disease is left untreated, within 10-20 years the degeneration progresses, and patients are at risk for early death due to disease complications.

With recent advancements in pharmaceutical research, gene therapy is now a real hope for treating Parkinson’s Disease. In gene therapy, specific genes are targeted within a patient’s cells to create a therapeutic effect. Through this genetic technology, scientists have made strides in identifying therapies that are aimed at managing and eventually curing PD.

In this article, we will explore gene therapy and its potential in treating Parkinson’s Disease. We will discuss the different techniques used in gene therapy, the potential risks associated with it, animal models for Parkinson’s Disease, and the current clinical trials for gene therapy in PD. By the end of this article, readers should have a better understanding of how gene therapy can be used to treat Parkinson’s Disease.

Reprogramming a Patient’s Own Cells to Treat Parkinson’s Disease

Gene therapy as a treatment for Parkinson’s Disease utilizes ex vivo and in vivo methods to harness the power of the patient’s own cells. Ex vivo, cells extracted from the patient are reprogrammed to alter gene expression of specific Parkinson’s Disease-related genes. In vivo, these cells are reintroduced into the patient’s brain to provide neurorestorative and neuroprotective effects of the treatment. This combination of cell and gene delivery makes use of one of two delivery systems: viral or non-viral vectors.

Viral vectors commonly used in gene therapy are adenovirus, adeno-associated virus (AAV), herpes simplex virus, lentivirus, retrovirus, and Pox virus. These viruses are utilized because they allow researchers to take advantage of viral size and machinery to control how genes are delivered. Researchers create delivery systems that account for the size of the virus, genome, packaging capacity, transduction efficiency, integration, gene expression, and immunogenicity to determine the best delivery system for the tissue of interest to treat the disease. Non-viral vectors use naked plasmid DNA and inorganic chemical particles. They have lower efficiency when compared to viral vectors and lower expression. Depending on the specific purpose, the different types of gene delivery systems are used at different stages of therapy development to target either disease-modifying genes or non-disease-modifying genes associated with Parkinson’s disease.

In addition to the selection of the gene delivery system, there are important regulatory considerations that require an assessment of the gene delivery system and the potential risks to the patients. These regulatory considerations require an efficacy assessment of the dosage, transfection efficiency, treatment duration, route of administration, and site of administration. Furthermore, it is necessary to consider the treatment safety especially when cells are taken from ex vivo stage and reintroduced into the patient in vivo.

Targeting Disease-Modifying & Symptom-Modifying Genes in PD

The promise of gene therapy for Parkinson’s Disease (PD) lies in its ability to specifically target the underlying cause of the disease and reverse its progress at a molecular level. To date, several gene targets have been identified as potential disease-modifying agents, with the most promising genes functioning as neurotrophic factors. Neurotrophic factors are molecules that, when delivered to the brain, can promote the survival and differentiation of neurons. These genes include Brain-derived neurotrophic factor (BDNF), and Cerebral dopamine neurotrophic factor (CDNF), Glial cell line-derived neurotrophic factor (GDNF), and neurturin (NTN) (Axelsen et al, 2018).

While symptom-modifying genes focus on dopamine synthesis and dopamine transporters to increase the production and transport of dopamine within surviving neurons in the patient’s brain. These genes include tyrosine hydroxylase, aromatic amino acid decarboxylase (AADC), glutamic acid decarboxylase (GAD1), and GTP cyclohydrolase 1 (GCH). The potential for gene therapy to target the underlying causes of non-motor symptoms of PD has revealed a range of possibilities for improving the quality of life of patients with PD. The targeted delivery of genes to increase dopamine levels can help mitigate the effects of the disease and provide relief from the debilitating symptoms. Although the development of gene therapy in PD is still in its early stages, the potential to improve the quality of life of patients is an exciting prospect. Luckily, Parkinson’s Disease can be modeled in animals to determine the safety and efficacy of gene therapeutics. We further describe these models and how Anilocus provides Sponsors with preclinical solutions to investigate their treatments for Parkinson’s Disease.

Clinical Trials and the Gene Therapy Competitive Landscape for PD

The potential of gene therapy to treat Parkinson’s disease has been a topic of great research and interest for quite some time with novel therapeutic technologies regularly introduced into clinical trials. While much of the research is still in the preclinical phase, gene therapy has been making steady progress toward becoming a viable option for PD. Many clinical trials have been conducted to assess the safety and efficacy of gene therapy for the treatment of PD.

In the United States, at least eight Sponsors are in clinical trials for gene therapies for Parkinson’s Disease: Brain Neurotherapy Bio, Genzyme (Sanofi), MeiraGTx, Neurologix. With collaborations between Sangamo Therapeutics/Ceregene, and Voyager Therapeutics/Neurocrine Biosciences. The most common targets were three neurotrophic factors: AADC, GDNF, NTN and GAD with AAV and AAV2 viral vectors selected for gene delivery.

As these treatments move through the clinical trial process, researchers and clinicians are gaining more information about the safety and efficacy of gene therapy and the potential risks associated with the treatments. With the increasing number of gene therapy companies entering the market, the competitive landscape is rapidly evolving.


Gene therapy has the potential to revolutionize the treatment of Parkinson’s Disease, offering a novel approach to treating the disease and potentially restoring function. The use of gene therapy techniques, such as genome editing, viral vector delivery, non-viral vector delivery, and neurotrophic factors, allows for the specific targeting of genetic markers of the disease. The identification of disease-modifying and symptom-modifying genes in PD has opened the possibility of using gene therapy to target the underlying cause of the disease and to improve the symptoms associated with it.

Preclinical animal studies have shown promise in the use of gene therapy to treat PD. These studies have identified key brain regions involved in Parkinsonian behaviors and have tested the safety and efficacy of gene therapy in various species of animals. To further assess the efficacy of gene therapy, several clinical trials have been initiated and at least two have successfully completed Phase I Clinical Trials. While two studies sponsored by Neurologix showed clinical benefit in a Phase II trial assessing bilateral subthalamic infusions of NLX-P101 (AAV2-GAD) but were terminated after Neurologix declared bankruptcy in March 2012 (Bloomberg, 2012; Niethammer et al, 2017).

The potential implications of gene therapy for patients are vast and exciting. Functional recovery is becoming a reality for many, and these clinical benefits offer hope to those living with the disease. In addition, the competitive landscape for gene therapy in PD is rapidly expanding, opening the door to different treatment options for Sponsors to either become the first to market or the best on the market.


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