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.
Many people with Parkinson’s disease have been carefully watching the development of gene therapies and trophic factors for the potential treatment of Parkinson’s disease. Trophic factors are proteins that are important to cell development. Trophic factors have also been thought to play a critical role in promoting brain cell survival. A few years ago, glial cell derived neurotrophic factor (GDNF) was pumped into Parkinson’s disease brains, however this therapy was not proven to have a robust clinical effect, and in some cases was associated with unacceptable adverse events. A few months ago, a pill called Cogane, another neurotrophic factor therapy, failed in a human trial including Parkinson’s disease patients. A few weeks ago an announcement was made that the CERE-120 Neurturin trial of a different neurotrophic factor, failed. We will in this month’s What’s Hot column review the recent trial results, and we will discuss the potential implications for the field.
CERE-120 was a trial that utilized an adeno-associated virus to deliver a protein to the brain. The protein was called Neurturin. The idea of the trial was to attempt to rescue some of the dying brain cells, and to improve motor function. In the first pilot trial, which was conducted a few years ago, neurosurgeons drilled small holes into the skulls of patients and then inserted the therapy through a pipe called a guide cannula. The neurosurgeons placed the Neurturin therapy directly into a brain structure called the putamen. The trial results indicated that there was no benefit for Neurturin when compared to placebo injections at the 12 month time point, but there was a possible benefit when following patients out as far as 15 months. The investigators decided to repeat the trial, increase the dose of Neurturin and to deliver it into two brain locations; the putamen and the substantia nigra. The investigators also decided to lengthen the follow-up period to 15 months to account for possible delayed benefits that may have been missed on the pilot trial. The primary outcome, which was the improvement in Parkinson’s disease motor scores, was not achieved.
Should the results of the CERE-120 Neuturin and other neurotrophic factor trials be a complete disappointment to the Parkinson’s disease community. I would argue, no, it is not completely disappointing. First, this trial demonstrated the safety of using adeno-associated gene therapy in human patients and this has now been performed several times in real Parkinson’s disease patients. The ability to safely deliver trophic factors such as Neuturin using gene therapy will be important for future trials with various novel therapeutic agents. Second, we learned a great deal about delivery systems and how hard it is to get any therapy across the blood-brain barrier. The blood-brain barrier is designed to protect the brain, but it has introduced significant challenges for the therapeutic development of drugs targeting Parkinson’s disease symptoms. Finally, we were humbled that despite promising animal trials, human trials did not pan out.
Though trophic factor treatment for Parkinson’s disease suffered a setback with the recently announced results of the CERE-120 Neurturin trial, it should be kept in perspective that there are many trophic factors in the human brain, and that there are many potential approaches to using these factors to advance a new therapy for Parkinson’s disease.
Posted: 5/2/2013 9:56:02 AM by
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.
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Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step
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The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team
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Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach
Does it Matter if I Can’t Get Brand Sinemet?
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism
Calling for the FDA to Revise the Eight Sinemet a Day Rule
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?
Is the PD SURG Trial Another Surge Forward for DBS Therapy?
Cycling in PD in Those Who Can’t Walk: Is it Possible?
New iPS Stem Cells for PD: What Does it Mean?
Time for Comprehensive Care Networks for PD
Is Parkinson's Disease a Prion Disease?
Parkinson's Disease Linked to Gaucher's Disease
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies
Is it Safe to Have an MRI with a DBS in Place?
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms
Keeping an Eye on Trials Important to the Parkinson's Disease Patient
Increased Risk of Melanoma in Parkinson's Disease
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?
Is Exercise Effective Treatment and Protection Against PD?
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?
Update on Gene Therapy for Parkinson's Disease