Glial cell line–derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) 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. This study warrants careful examination of GDNF as a treatment for Parkinson disease.
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We thank Amgen for providing the GDNF and information on their previous GDNF infusion trial; M. Traub for critical reading of this manuscript; the Parkinson Disease Society (UK) for a support grant towards equipment and salary; M. Klein and B. Schultz for discussions and technical support; D. Kistler for help with the statistical analysis; G. Gerhardt and D. Gash for sharing unpublished data; and A. Björklund and O. Lindvall for discussions regarding this trial.
The authors declare no competing financial interests.
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Gill, S., Patel, N., Hotton, G. et al. Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease. Nat Med 9, 589–595 (2003). https://doi.org/10.1038/nm850
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