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.
You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.