What is gene therapy? Can it benefit Parkinson’s disease?

Gene Therapy for Parkinson’s disease

You may have read about efforts to use gene therapy as a treatment for Parkinson’s disease (PD).  It’s an exciting prospect and studies are underway, with some positive results so far. Understanding these studies and therapies requires some background information about what genes are and how they work, so I’ve included a glossary at the end of this article. You might find it helpful to scroll down and get familiar with the terminology before reading the rest of the article.

The promise of gene therapy

Gene therapy is a category of treatments that involve introducing DNA into cells in an effort to alter which proteins are created and thereby improve symptoms or even cure disease.

For decades, researchers have been trying to perfect gene therapy treatments for a variety of conditions, but progress has been slow. There have been successes for certain rare genetic disorders which are characterized by a single, well-described mutation in a particular gene. In this situation, a healthy gene is introduced into the cells of these patients. The cell’s machinery then uses the healthy gene to create a healthy protein, which can effectively cure the patient. Diseases that have been helped in this manner include severe combined immune deficiency, adenosine deaminase deficiency, and hemophilia.

It is much more difficult to attempt gene therapy for diseases that involve more complicated DNA changes. Nevertheless, there has been much effort and some success in using gene therapy techniques to treat cancer, for example, a very complex disease which typically involves many genetic changes.

How gene therapy works

A virus is a tiny bundle of nucleic acid that is able to penetrate a cell and hijack the cell’s machinery to replicate its own nucleic acid as well as produce viral proteins, often causing disease in the process. Certain viruses are even able to incorporate their own genetic material into the genetic material of the cell that they infect. Scientists cleverly take advantage of these processes to drive gene therapy. The harmful pieces of DNA are removed from the virus and the gene of choice is incorporated into the viral structure. Then the modified virus is injected into a specific part of the body, thereby allowing it to “infect” cells. If all goes according to plan, the piece of DNA that was introduced into the modified virus is used by the cell’s machinery to make the protein of choice.

Gene therapy for Parkinson’s disease

There have been a number of clinical trials that used various gene therapy strategies to treat PD. These have included the following:

  • Glutamic acid decarboxylase (GAD) is an enzyme that increases the production of a brain chemical called gamma-aminobutyric acid or GABA. A gene for GAD was introduced into the subthalamic nucleus in the brains of patients with PD. The goal was to increase the presence of GABA in that brain area, thereby helping to reset the abnormal circuitry of the Parkinson’s brain.
  • Aromatic amino acid decarboxylase (AADC) is an enzyme important in the conversion of Levodopa to dopamine and the decline of AADC in the PD brain may be responsible for the changes in efficacy of long term Levodopa treatment. A gene for AADC was introduced into the putamen in the brains of patients with PD. The goal was to increase the amount of AADC present, thereby making Levodopa treatment more effective.
  • Neurturin (NTN), Glial derived neurotrophic factor (GDNF) – Neurturin is a protein that is a member of the GDNF family of nerve growth factors. A gene for Neurturin was introduced in different brain regions in patients with PD, with the goal of supporting the survival of neurons.
  • Tyrosine hydroxylase, Guanosine triphosphate cyclohydrolase, and Aromatic amino acid decarboxylase (TH-GCH-AADC) are three enzymes important in the synthesis of dopamine. Genes for all three enzymes were introduced into the putamen of patients with PD, with the goal of increasing dopamine production.


In general, the published trials of these compounds have showed modest improvements in functioning as measured by the United Parkinson Disease Rating Scale, which is promising. These gene therapy trials and their results are discussed in this article and summarized in this table.

What is the future of gene therapy for Parkinson’s disease?

The jury is still out on each of the gene therapy strategies discussed above and each is still under investigation in an active clinical trial, although as of publication of this blog, none are currently recruiting participants. Three of APDA’s Centers for Advanced Research are participating in gene therapy trials for Parkinson’s disease. Emory University School of Medicine and the University of Alabama at Birmingham School of Medicine are participating in trials of Neurturin. The University of Pittsburgh Medical Center and Emory University School of Medicine are participating in trials of AADC.

Tips and take-aways

  • There are four gene therapy strategies which are currently being studied in clinical trials. Each has promising data behind it and additional studies are underway.
  • If you are interested in joining a gene therapy clinical trial, keep your eye on clinicaltrials.gov to see if there are any that are recruiting patients. If you find one that interests you, talk with your neurologist about your suitability for such a trial.


Nucleotides –the molecules that serve as the building blocks for DNA and RNA

DNA: Deoxyribonucleic acid – large molecules consisting of two chains of nucleotides strung together and coiled to form a double helix shape. The molecule can replicate itself and contains biological information to make proteins needed for every aspect of life

Gene: a region of DNA that is used as a template to create a protein that influences biological function

Mutation: a change, often heritable, in one or more nucleotides within a gene that can affect the production of a protein

Chromosome: The larger structures into which DNA is organized. There are 46 chromosomes in all human cells (except in eggs and sperm cells where there are 23 chromosomes)

RNA: Ribonucleic acid – molecules that transfer information from the DNA and facilitate the creation of protein molecules

Protein: molecules consisting of a string of amino acids which are synthesized using the code embedded in DNA

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Dr. Rebecca Gilbert

APDA Vice President and Chief Scientific Officer

Dr. Gilbert received her MD degree at Weill Medical College of Cornell University in New York and her PhD in Cell Biology and Genetics at the Weill Graduate School of Medical Sciences. She then pursued Neurology Residency training as well as Movement Disorders Fellowship training at Columbia Presbyterian Medical Center. Prior to coming to APDA, she was an Associate Professor of Neurology at NYU Langone Medical Center. In this role, she saw movement disorder patients, initiated and directed the NYU Movement Disorders Fellowship, participated in clinical trials and other research initiatives for PD and lectured widely on the disease.

A Closer Look ArticlePosted in Parkinson's Treatments

DISCLAIMER: Any medical information disseminated via this blog is solely for the purpose of providing information to the audience, and is not intended as medical advice. Our healthcare professionals cannot recommend treatment or make diagnoses, but can respond to general questions. We encourage you to direct any specific questions to your personal healthcare providers.