Safety Study of Subthalamic Nucleus Gene Therapy for Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00195143
Recruitment Status : Completed
First Posted : September 19, 2005
Last Update Posted : March 27, 2008
Weill Medical College of Cornell University
North Shore University Hospital
Information provided by:
Neurologix, Inc.

September 15, 2005
September 19, 2005
March 27, 2008
August 2003
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Same as current
Complete list of historical versions of study NCT00195143 on Archive Site
  • Improvement in brain metabolism measured by PET scans
  • Improvement in standard clinical rating scales
Same as current
Not Provided
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Safety Study of Subthalamic Nucleus Gene Therapy for Parkinson's Disease
Phase I Study of Subthalamic GAD Gene Transfer in Medically Refractory Parkinson's Disease Patients
The purpose of this study is to determine the safety of using a modified virus to transfer a gene called GAD into a region of the brain called the subthalamic nucleus in patients with advanced Parkinson's disease. The overall goal of this approach is to ultimately normalize the flow of information in several brain regions responsible for movement, to ultimately improve function in patients with this disorder. The current study is primarily designed to evaluate the safety of this approach, but patients are also being monitored for possible signs of effectiveness as well.
This study involves treatment of patients with medically refractory Parkinson's disease (PD) with gene therapy. The patients are chosen from a population of patients who would normally be candidates for standard deep brain stimulation (DBS) surgery for PD. These patients respond to medical therapy, but develop substantially reduced responses over time, often with severe fluctuations in their condition between a functional and severely non-functional state. Some patients also develop dose-limiting side effects from medication, including involuntary movements called dyskinesias and nightmares. When there are no medical contraindications, DBS is often performed in these patients to try to quiet hyperactive brain regions such as the subthalamic nucleus (STN). In PD, the STN is overactive due to a loss of GABA inputs to this region, which normally reduces neuronal firing. In turn, the STN drives other brain regions, including the globus pallidus (GPi) and substantia nigra (SNr), which are also hyperactive and which also have reduced GABA inputs. The goal of this gene therapy trial is to introduce the gene for glutamic acid decarboxylase (GAD) into the STN using an adeno-associated virus (AAV) vector, in order to permit the STN to produce it's own GABA, as well as release GABA into the GPi and SNr targets, which also have reduced GABA inputs. This is anticipated to restore a more normal pattern of information flow from this basal ganglia circuit to the thalamus and higher cortical structures in order to reduce the motor symptoms of PD, while eliminating complications arising from inserting DBS electrodes and batteries into the human body.
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Parkinson's Disease
Genetic: Surgical infusion of AAV-GAD into the subthalamic nucleus
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
August 2005
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Inclusion Criteria:

  • Duration of disease: Greater than 5 years
  • Idiopathic Parkinson's disease
  • Parkinson's medication stable for 3 months
  • Absence of dementia
  • Hoehn and Yahr rating: 3 or greater and/or UPDRS: 30 or more in "off" state and/or Complications of l-dopa therapy limiting effective use

Exclusion Criteria:

  • Poor candidate for any surgery
  • Significant dementia
  • Secondary parkinsonism
  • Severe autonomic symptoms
  • Atypical Parkinson's disease
  • History of substance abuse
Sexes Eligible for Study: All
25 Years to 75 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
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Neurologix, Inc.
  • Weill Medical College of Cornell University
  • North Shore University Hospital
Principal Investigator: Michael G Kaplitt, MD PhD Weill Medical College of Cornell University
Principal Investigator: Matthew J During, MD Weill Medical College of Cornell University
Neurologix, Inc.
September 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP