Gene therapy for Parkinson's disease to be tested

February 22, 2016
Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

Experts at the University of Pittsburgh School of Medicine are leading the second arm of a clinical trial using gene therapy to relieve the symptoms of tremor and mobility impairment in patients with Parkinson's disease. The technique shows promise in prolonging the effectiveness of levo-dopa, the mainstay treatment for the progressive neurodegenerative condition, by increasing production of a key enzyme essential to convert the drug into the neurotransmitter dopamine.

An estimated 7 to 10 million people worldwide have Parkinson's disease, which is caused by degeneration of dopamine-producing neurons, said Mark Richardson, M.D., Ph.D., assistant professor of neurological surgery, Pitt School of Medicine, and director of Epilepsy and Movement Disorders Surgery at UPMC. Levo-dopa can replace the deficient dopamine for a while, but eventually the drug loses effectiveness, and subsequent increases in dosage may cause disabling side effects.

"Less dopamine is made as the neurons degenerate, and one reason is that there is a decrease in an enzyme needed to turn levo-dopa into dopamine," said Dr. Richardson, who is the principal investigator of the Pitt arm of the trial. "By inserting the gene for this enzyme into cells in a specific part of the brain, we hope to make levo-dopa treatment more effective for a longer period of time."

In the , a harmless virus called adeno-associated virus-2 is used to carry the gene that makes the enzyme – aromatic L-amino acid decarboxylase (AADC) – into neurons. Once in the neurons, cellular machinery kicks into gear to increase production of the AADC enzyme.

To deliver the treatment, Dr. Richardson will make a small hole in each side of the patient's skull to insert a thin catheter into the putamen, a brain region that is an important part of the circuit affected by Parkinson's disease. After the gene therapy is infused over several hours, the catheter is withdrawn and the skull is repaired.

Different infusion doses will be tested during the course of the study. Up to 20 participants at two sites, Pittsburgh and San Francisco, will be followed for up to three years to have their disease and medication status reassessed.

The principal investigator of the trial, which is sponsored by Voyager Therapeutics, is Krystof Bankiewicz, M.D., Ph.D., of the University of California, San Francisco, who also led an earlier trial that showed the gene therapy can be safely administered.

Explore further: Gene therapy prevents Parkinson's disease in animal model

More information: Individuals between 40 and 70 who have had Parkinson's disease for more than five years and have been taking levo-dopa for at least three years may be eligible to participate in the trial. For more information, contact Patricia Porter, B.S., at 412-648-8983 or Porterpm2@upmc.edu.

Related Stories

Gene therapy prevents Parkinson's disease in animal model

June 15, 2015

Gene therapy to reduce production of a brain protein successfully prevented development of Parkinson's disease in an animal study, according to researchers at the University of Pittsburgh School of Medicine. The findings, ...

Major complication of Parkinson's therapy explained

September 10, 2015

Researchers have discovered why long-term use of L-DOPA (levodopa), the most effective treatment for Parkinson's disease, commonly leads to a movement problem called dyskinesia, a side effect that can be as debilitating as ...

Researchers uncover how dopamine transports within the brain

January 25, 2016

Researchers at University of Florida Health have discovered the mechanics of how dopamine transports into and out of brain cells, a finding that could someday lead to more effective treatment of drug addictions and neurological ...

Ending chronic pain with new drug therapy

December 21, 2015

A brain region controlling whether we feel happy or sad, as well as addiction, is remodeled by chronic pain, reports a new Northwestern Medicine study.

Recommended for you

Parkinson's disease patients benefit from physical activity

November 15, 2016

A comprehensive review published in the Journal of Parkinson's Disease confirms that people living with Parkinson's disease (PD) can benefit from being physically active, especially when it comes to improving gait and balance, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.