GDNF - Back in the clinic

This paper aims to evaluate in PD the efficacy and safety of intermittent GDNF intra-putaminal infusions administered by Convection Enhanced Delivery. In animal models of PD and in open label studies in PD patients, continuous intra-putaminal GDNF infusions have been shown to improve motor symptoms and, as assessed by 18F-dopa PET and post-mortem assessments, restore dopamine terminals. However, in 2003, a placebo-controlled multi-centre trial reported failure to demonstrate clinical benefit, despite improvements in PET end-points. In addition, a concurrent study in monkeys raised questions over safety. Since that point no further human investigations have been performed. In significant part, we believe, the above issues were due to a failure in the way GDNF was surgically delivered. We have now developed an in-house device which animal model studies suggest will allow GDNF to be given much more reliably to the putamen. We feel this allows for definitive testing of GDNFs effects in humans. This will be the first clinical study of intermittent GDNF infusions delivered by CED in man.