You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration.

Note: You can also watch Dr. Okun address this topic in a video appearing at the end of this blog entry.

Hailed as a major breakthrough for Parkinson’s disease research, investigators from multiple institutions throughout the United States published an important paper on gene therapy in March 2011. The study was a double-blind (neither the investigators nor the patients knew which patients were receiving the real treatment) randomized trial, and was one of the largest of its type to be performed in actual Parkinson’s disease patients. The study utilized a clever and novel technology in order to change the nature of a nucleus in the brain called the subthalamic nucleus, which in PD becomes overactive leading to the movement disorders characteristic of the condition.  The nucleus normally infuses excitatory chemicals into the brain, but was converted to infuse inhibitory chemicals. The investigators accomplished their goal by utilizing gene transfer of glutamic acid acid decarboxylase, or GAD into the subthalamic nucleus region. This technique was performed on two sides of each participant’s brain, and some patients received a sham surgery (a mock procedure designed to mimic the experimental approach). Although the results were not as robust as what has been observed with deep brain stimulation and with other therapies, the door seems to have swung open for gene therapy approaches in Parkinson’s disease.

The study included patients between the ages of 30 and 75 years who had a diagnosis of Parkinson's disease, and a very good response to levodopa therapy. Seven centers participated from across the United States. The study used a novel technology to apply gene therapy at the bedside, rather than in an operating room setting. Motor scores on a scale called the UPDRS were used as the primary outcome. Sixty-six patients were included in the study, and 23 were assigned to receive sham surgery and 22 assigned to gene therapy infusion. What is interesting about this study was that the investigators designed a completely sham procedure in order to be sure that there was a difference between the gene therapy group, and the sham operated group. The motor scores improved by eight points in the gene therapy group, and by nearly 5 points in the sham group. This was a significant difference favoring the gene therapy group. Only 21 sham surgery patients and 16 gene therapy patients of the original 66 were analyzed for primary outcomes meaning that the study was smaller than one may have hoped for.  Importantly, the adverse event and safety profile were reported as excellent, with the most common side effect being headache (seven patients in the gene therapy group and only two in the sham group complained of this  symptom). The study authors felt that this therapy should be further explored for Parkinson’s disease.

Though the results of this study were positive, patients should not come away with false impressions and with false hopes. This type of gene therapy was targeted as a symptomatic approach to address levodopa responsive Parkinson's disease issues. It was not a neuroprotective approach, nor was it a disease modifying approach. The benefits were mainly mild improvements in the motor symptom scale. Though the therapy fared better than sham, it did not perform better than deep brain stimulation performed in the same target (as reported by other recent studies).

The future of gene therapy for Parkinson's disease we hope will be bright. The lessons from early studies such as the one published in Lancet Neurology should point us in the right direction. Larger numbers of patients will need to be examined, outcomes optimized, and safety documented. There is an overriding concern for the future of gene therapy in long-term delayed adverse events, and we will need to carefully document their presence or absence. The transplant trials in Parkinson’s disease patients taught us important lessons including the appearance of delayed complications, one of which runaway dyskinesia, proved to be a limiting issue for continuation of the therapy.

Hopefully gene therapy approaches can be modified to address non-medication responsive symptoms of Parkinson's disease. Remember, this current gene therapy approach was aimed at achieving symptomatic improvement of levodopa responsive Parkinson's disease symptoms. The field remains however, in desperate need of therapies targeting both motor and non-motor symptoms that are resistant to levodopa and other therapies. These symptoms include but are not limited to walking, balance, speech, swallowing, cognition, mood, and sexual dysfunction.

We remain very encouraged about gene therapy and its possibilities for future use in Parkinson’s disease patients. This study will hopefully help to open some doors and to challenge our scientists to continue to develop and to continue to refine techniques that will target the symptoms that matter the most to our patients with Parkinson disease, mainly the levodopa resistant symptoms.


Lewitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Van Meter L, Sapan CV, During MJ, Kaplitt MG, Feigin A. AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind,sham-surgery controlled, randomised trial. Lancet Neurol. 2011 Mar 16. [Epub ahead of print] PubMed PMID: 21419704. 


Posted: 4/1/2011 6:03:37 AM by Cathy Whitlock

Browse current and archived What's Hot in PD? articles, the National Parkinson Foundation's monthly blog for people with Parkinson's written by our National Medical Director, Dr. Michael S. Okun. 

June 2015
Short and Long-Term Problems with Anticholinergic Drugs used for Sleep, Bladder, and Tremor Symptoms

May 2015
Leaps in Deep Brain Stimulation Technology

April 2015
What to tell Parkinson’s patients about diet and taking statin drugs

March 2015
Everything a Parkinson’s Disease Patient Needs to Know About the New Dopamine Pump

February 2015
Tips for Parkinson’s Disease Patients Switching from Sinemet or Madopar to Rytary (IPX066)

January 2015
More Evidence Linking Gut Bacteria to Parkinson’s Disease: A Guide for Patients

December 2014
Two New Therapies for Parkinson’s Disease Patients to get Excited About: Vaccines and Monoclonal Antibodies

November 2014
The Importance of a Monitoring Strategy When Prescribing Dopamine Agonists: Lessons from the National Parkinson Foundation Data

October 2014
Is Midlife Migraine Related to Late Life Parkinson’s Disease?

September 2014
Deep Brain Stimulation for Parkinson’s Disease: NPF Congratulates Mahlon DeLong and Alim-Louis Benabid and Looks to a Bright Future in Human Neural-Network Modulation

August 2014
Everything You Need to Know About Medical Marijuana and Parkinson’s Disease

July 2014
The End for Levodopa Phobia: New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson's Disease

June 2014
Is light therapy a potential treatment modality in Parkinson’s disease?

May 2014
How does the most common genetic cause of Parkinson’s Disease (LRRK2) cause Parkinson’s disease and could it be used to help develop a better therapy?

April 2014
An Update on DAT Scanning for Parkinson’s Disease Diagnosis

March 2014
Could Northera (Droxidopa) Be an Alternative Treatment for Low Blood Pressure and Passing Out Symptoms?

February 2014
The Dream of a Pill Free Existence and the Continuous Dopaminergic Pump for the Treatment of Parkinson's Disease

January 2014
Should I take Inosine to Raise my Uric Acid Levels and Treat my Parkinson’s Disease?

December 2013
Could Fungus and Mold be an Important Contributor to Parkinson’s Disease?

November 2013
Pimavanserin and the Hope for a Better Drug for Hallucinations and Psychosis in Parkinson’s Disease

October 2013
Halting of the Creatine Study

September 2013
The Importance of Identifying and Treating Caregiver Strain

August 2013
Putting Parkinson’s Disease Information into the Palm of Your Hand: Parkinson’s Enters the Smartphon

July 2013
What Parkinson’s Disease Patients Need to Know about H. Pylori Gastrointestinal Infections

June 2013
A2A Receptor Antagonists and Parkinson’s Disease Treatment

May 2013
Another Setback for Trophic Factor Treatment in Parkinson's Disease

April 2013
IPX066 and What Patients Really Want in New Carbidopa/Levodopa (Sinemet) Formulations

March 2013
The Weather Forecast for Parkinson’s Disease Calls for Worldwide Economic Storm

February 2013
Defeating the Barriers to Implementing Exercise Regimens in Parkinson’s Disease Patients

January 2013
When should you start medication therapy for Parkinson’s disease?

December 2012
Neurologist Care Reduces Hospitalizations in Parkinson's Disease

November 2012
A Victory in Court for Parkinson's Disease Patients who Require Ongoing Rehabilitative Therapies

October 2012
Given the recent FDA announcement about Mirapex (pramipexole), should I be worried about dopamine agonists?

September 2012
What about the new Parkinson’s Disease Vaccine? What should I know?

August 2012
Caffeine as a Potential Treatment for Parkinson’s Disease

July 2012
Time to Consider GPi DBS for Parkinson’s Disease: A Shift in the Practice of Patient Selection for DBS

June 2012
A New Treatment for Parkinson’s Disease-Related Constipation

May 2012
Too Many Pills: Improving Delivery Systems for Parkinson’s Disease Drugs

April 2012
Measuring Quality and Assessing Depression in Parkinson's Disease

March 2012
Watch out for Unexpected Obstacles if You Use a Cueing Strategy to Break Freezing of Gait in Parkinson’s Disease

February 2012
Pill Color, Generic Medications and Insurance Issues: Important Medication-Related Tips for the Parkinson’s Disease Patient

January 2012
Are Blood Tests for Parkinson’s Disease on the Horizon?

December 2011
Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step

November 2011
Important News for the Parkinson’s Disease Community: More Evidence that Sinemet and Madopar are Not Toxic and do Not Accelerate Disease Progression

October 2011
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team

September 2011
Scientists say Research on Brain Proteins Involved in Parkinson’s Disease is “Shaping” Up

August 2011
Who Actually Takes Care of Most of the Parkinson’s Patients Worldwide: The Need for Education and the Parkinson’s Toolkit

July 2011
If you are Dizzy or Passing Out, it could be Your Parkinson’s Disease or Parkinson’s Disease Medications

June 2011
How Will Group Visits for Parkinson’s Disease Fit into the Future of Parkinson’s Disease Care?

May 2011
Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease

April 2011
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach

March 2011
Does it Matter if I Can’t Get Brand Sinemet?

February 2011
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?

January 2011
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease

December 2010
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism

November 2010
Calling for the FDA to Revise the Eight Sinemet a Day Rule

October 2010
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease

September 2010
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts

August 2010
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research

July 2010
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management

June 2010
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?

May 2010
Is the PD SURG Trial Another Surge Forward for DBS Therapy?

April 2010
Cycling in PD in Those Who Can’t Walk: Is it Possible?

March 2010
New iPS Stem Cells for PD: What Does it Mean?

February 2010
Time for Comprehensive Care Networks for PD

January 2010
Is Parkinson's Disease a Prion Disease?

December 2009
Parkinson's Disease Linked to Gaucher's Disease

November 2009
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies

October 2009
Is it Safe to Have an MRI with a DBS in Place?

September 2009
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)

August 2009
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?

July 2009
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms

June 2009
Keeping an Eye on Trials Important to the Parkinson's Disease Patient

May 2009
Increased Risk of Melanoma in Parkinson's Disease

April 2009
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients

March 2009
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?

February 2009
Is Exercise Effective Treatment and Protection Against PD?

January 2009
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?

December 2008
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?

November 2008
Update on Gene Therapy for Parkinson's Disease

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Each month, we will feature a new column by NPF's National Medical Director, Dr. Michael Okun, on the latest developments in Parkinson's disease research. Read the latest "What's Hot in PD?" below.

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