Intraputamenal infusion of glial cell line–derived neurotrophic factor in PD: A two‐year outcome study
Annals of NeurologyPublished 24 January 2005
Nikunj K. Patel, Martin Bunnage, Puneet Plaha, Clive N. Svendsen, Peter Heywood, Steven S. Gill
Citations384
SJR quartileQ1
SJR score3.74
SNIP2.26
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
After 2 years of continual GDNF infusion, there were no serious clinical side effects and no significant detrimental effects on cognition and health‐related quality‐of‐life measures showed general improvement over time.
Abstract
We have shown previously that intraparenchymal infusion of glial cell line-derived neurotrophic factor (GDNF) continuously into the posterior putamen in five Parkinson's disease patients is safe and may represent a new treatment option. Here, we report a continuation of this phase I study. After 2 years of continual GDNF infusion, there were no serious clinical side effects and no significant detrimental effects on cognition. Patients showed a 57% and 63% improvement in their off-medication motor and activities of daily living subscores of the Unified Parkinson's Disease Rating Scale, respectively, and health-related quality-of-life measures (Parkinson's Disease Questionnaire-39 and Short Form-36) showed general improvement over time.
Keywords
Neuroscience
American Educational Research JournalStatistical Theories of Mental Test Scores
8,138 Citations1969William W. Rozeboom, Frederic M. Lord +2 more
ScienceGDNF: a Glial Cell Line-Derived Neurotrophic Factor for Midbrain Dopaminergic Neurons
3,238 Citations1993Leu‐Fen H. Lin, Daniel H. Doherty +3 more
In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake and did not increase total neuron or astrocyte numbers or transmitter uptake.
New England Journal of MedicineTransplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease
2,364 Citations2001Curt R. Freed, Paul Greene +10 more
After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.
Nature MedicineDirect brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease
1,294 Citations2003Steven S. Gill, Nikunj K. Patel +7 more
Positron emission tomography scans of [18F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function, and warrants careful examination ofGDNF as a treatment for Parkinson disease.
NatureProtection and repair of the nigrostriatal dopaminergic system by GDNF in vivo
1,091 Citations1995A. Tomac, Elisabet Lindqvist +5 more
It is concluded that intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease.
TRANSPLANTATION OF EMBRYONIC DOPAMINE NEURONS FOR SEVERE PARKINSON'S DISEASE
1,000 Citations2001Rachel Reed, P Aul E. G Reene +9 more
NatureFunctional recovery in parkinsonian monkeys treated with GDNF
964 Citations1996Don M. Gash, Zhiming Zhang +10 more
Evaluating the effects of GDNF injected intracerebrally into rhesus monkeys that have had the symptomatology and pathophysiological features of Parkinson's disease induced by the neurotoxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine indicates that GDNF may be of benefit in the treatment of Parkinson’s disease.
NeurologyRandomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD
814 Citations2003John G. Nutt, Kim J. Burchiel +10 more
GDNF administered by ICV injection is biologically active as evidenced by the spectrum of AE encountered in this study, and did not improve parkinsonism, possibly because GDNF did not reach the target tissues—putamen and substantia nigra.
NatureMesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain
662 Citations1995Klaus D. Beck, Janet Valverde +6 more
It is reported that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra, which suggests that GDNF or related molecules may be useful for the treatment of Parkinson's disease.
Annals of NeurologyClinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease
387 Citations1999Jeffrey H. Kordower, Stéphane Palfi +8 more
There was no evidence of significant regeneration of nigrostriatal neurons or intraparenchymal diffusion of the intracerebroventricular GDNF to relevant brain regions in a 65-year-old man with Parkinson's disease.
Neurobiology of DiseaseStudies on Neuroprotective and Regenerative Effects of GDNF in a Partial Lesion Model of Parkinson's Disease
246 Citations1997Anders Björklund, Carl Rosenblad +2 more
Administration of glial cell line-derived neurotrophic factor (GDNF) appears to be a particularly effective site for induction of axonal sprouting and regeneration accompanied by recovery of spontaneous sensorimotor behaviors in the chronically lesioned nigrostriatal dopamine system.
Journal of Neurology Neurosurgery & PsychiatryUsing the SF-36 measure to compare the health impact of multiple sclerosis and Parkinson's disease with normal population health profiles
130 Citations2003Afsane Riazi
The results highlight the need for further research into aspects of health measured by the SF-36, and suggest generic measures that are applicable across multiple diseases may fail to address clinically important aspects of the impact of specific disorders.
Journal of Neurology Neurosurgery & PsychiatryCognitive functioning after subthalamic nucleotomy for refractory Parkinson's disease
46 Citations2000RJ McCarter
Preliminary data on the first reported cognitive changes after subthalamic nucleotomy suggested few adverse cognitive effects of the surgery although discrete neuropsychological changes were seen in some patients.
Psychological AssessmentThree standard errors of measurement and the Wechsler Memory Scale--Revised.
15 Citations1991Leslie Atkinson