April 30, 2003
Laurie Barclay, MD
Continuous infusion of glial-derived neurotrophic factor (GDNF) is safe and effective at restoring function for patients with Parkinson's disease, according to a presentation at the American Association of Neurological Surgeons annual meeting in San Diego, California.
"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," senior author Steven S. Gill, MD, says in a news release. "Some of these patients may be helped with surgical treatments including deep brain stimulation and transplantation of dopamine neurons into the brain. But neither of these approaches is able to successfully cease the progressive loss of remaining dopamine neurons."
GDNF is a naturally occuring neurotrophic factor thought to be important in development and maintenance of dopaminergic neurons. In animal models of Parkinson's disease, intracerebral infusion of GDNF improves motor function.
In this phase I safety study, five patients with Parkinson's disease poorly controlled by optimal medical therapy had catheter implantation in the dorsal putamen for chronic infusion of human recombinant GDNF via indwelling pump.
The adverse effects of direct infusion of GDNF into the brain for more than one year were relatively minor. However, at higher concentrations of infusion, signal changes around the catheter tips were seen on magnetic resonance imaging (MRI), and the patients experienced L'Hermitte's phenomenon. When the dose was reduced after three months, both the MRI changes and L'Hermitte's phenomena improved.
After one year, all patients had clinical improvement in motor function (39%) and in activities of daily living (61%) subscale scores of the Unified Parkinson's Disease Rating Scale. Quality-of-life measures improved in all patients.
Dyskinesias secondary to dopamine replacement therapy were reduced by 64% in four of five patients who experienced this symptom. There were no dyskinesias off medication or significant changes in cognitive function at the end of one year. Surprisingly, three patients who had long-standing loss of smell and taste recovered these sensations within a few weeks of starting treatment.
At 18 months, positron emission tomography scans showed an increase in dopamine storage by 28% in the putamen and by 16% to 26% in the substantia nigra, suggesting a direct effect of GDNF on dopamine function.
Although these results are promising, the authors recommend a phase II trial with full blinding.
"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," says lead author Nikunj K. Patel, MD.
AANS Annual Meeting: Abstract 847. Presented April 30, 2003.
Reviewed by Gary D. Vogin, MD
© 2003 Medscape