Glial Derived Neurotrophic Factor

Glial-derived neurotrophic factor (GDNF; Amgen Inc.) is a recombinant neuropeptide, which may promote survival or regenerate dopaminergic neurons. Open-label reports of continuous infusion directly into the putamen reported improvement in UPDRS motor scores and on time (37). Lang et al. (38) reported a 34-patient randomized trial of bilateral continuous GDNF infusion, 15 ^g/putamen/day or placebo. At six months, the mean percentage improvements in off UPDRS motor score were 10.0% with GDNF and 4.5% with placebo (P = 0.53). Secondary endpoint results were similar between the groups. A positron emission tomography (PET) scan analysis revealed a 32.5% treatment difference favoring GDNF in the mean 18F-dopa influx constant (P = 0.019). These results led to the discontinuation of further development of this drug by Amgen. However, GDNF continues to create enthusiasm in some researchers who posit that differences in the delivery systems may account for the discordant results. Alternative methods of delivery, including viral vector delivery and encapsulated cell delivery systems, are also under development for this and other nerve growth factors such as CERE-120 (Neurturin) (39,40).

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