Potential Treatment for Parkinson's Disease

More than one million Americans suffer from Parkinson's disease, a progressive degeneration of the nervous system. The disease occurs when certain brain cells, or neurons, stop producing the chemical messenger dopamine and in its absence the brain's ability to generate and coordinate movements is impaired. A new study "Direct Brain Infusion of Glial Cell Line-Derived Neurotrophic Factor in Parkinson Disease," is being presented during the 71st Annual Meeting of the American Association of Neurological Surgeons (AANS) in San Diego.

The study, highlighting a new treatment option for Parkinson's disease, will be presented by Steven S. Gill, MD; Nikunj K. Patel, MD; Gary R. Hotton, MD; Karen O'Sullivan, MD; Renee McCarter, MD; Martin Bunnage, MD; David J. Brooks, MD; Clive N. Svendsen, MD, and Peter Heywood, MD, on Wednesday, April 30, from 3:45 to 4 p.m.

"The mainstay of treatment for patients with Parkinson's disease is oral dopamine replacement, but as the disease progresses patients become less responsive to this medication. Some of these patients may be helped with surgical treatments including deep brain stimulation and transplantation of dopamine neurons into the brain," said Steven S. Gill, MD, co-author of the study and AANS member. "But neither of these approaches is able to successfully cease the progressive loss of remaining dopamine neurons."

Glial Cell Line-Derived Neurotrophic Factor (GDNF) is a naturally produced growth factor, which is thought to be important for the development and maintenance of dopamine neurons. In animal models of Parkinson's disease, its infusion into the brain has been shown to improve their motor function.

In this study, the authors selected five patients with Parkinson's disease who were poorly controlled despite best medical therapy. In this phase I safety study, the authors delivered GDNF directly into the patient's brains via catheters implanted in their putamen, an area of the brain that is deprived of dopamine in Parkinson disease. GDNF was delivered by a pump that was implanted in the abdominal wall and refilled on a monthly basis.

The side effects of direct infusion of GDNF into the brain were relatively minor, although at higher concentrations of infusion, signal changes were seen around the catheter tips on MRI scans and the patients experienced intermittent tingling in the neck and shoulders (L'hermitte's phenomenon). Because this was a safety study the dose was reduced after three months and both the MRI changes and L'hermitte's phenomena improved.

After one year, all patients had shown clinical improvement in their motor function (39%) and their ability to carry out normal activities of daily living (61%). Dyskinesias (involuntary movements) that occur as a result of dopamine replacement therapy were improved in the 4/5 patients in whom they were a problem (64% reduction). The authors did not observe dyskinesias in these patients when they were off medication, which has been seen, in recent trials of dopamine neuron transplantation. There were no significant changes in cognitive function at the end of one year, but quality of life measures were improved in all patients.

Positron Emission Tomography (PET) scans showed that in the area where GDNF was infused, there was an increase in dopamine storage (28% at 18 months) suggesting a direct effect of GDNF on dopamine function.

An unexpected effect was that three patients who had long-standing loss of the sensations of smell and taste, (which is not uncommon in Parkinson's disease), recovered these sensations within a few weeks.

This open labeled study shows for the first time that direct intra-putamenal GDNF infusion in patients with Parkinson's disease can be tolerated for at least one year, and that the treatment leads to improvement in motor function as well as increases in dopamine storage in the putamen. While the results of this study are promising, the authors emphasize that a phase 2 trial with full blinding is now required.

"Our hope is that this study will prompt further research into the use of other neurotrophins which may have the potential to slow down the progression or promote recovery of neurons in other neurodegenerative disorders including Alzheimer's disease and Huntington's disease," said Nikunj K. Patel, MD, co-author of the study and AANS member.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,500 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system including the spinal column, spinal cord, brain and peripheral nerves.