Trials of GDNF in Parkinson’s disease have yielded inconsistent results. In a randomised controlled trial, Whone
et al.
administer GDNF using a paradigm designed to optimize delivery to the putamen. [
18
F]DOPA PET reveals putamen-wide uptake, but GDNF does not differ from placebo in its effects on motor function.
Background: Intraputamenal glial cell line-derived neurotrophic factor (GDNF), administered every 4 weeks to patients with moderately advanced Parkinson's disease, did not show significant clinical improvements against placebo at 40 weeks, although it significantly increased [ 18 F]DOPA uptake throughout the entire putamen. Objective: This open-label extension study explored the effects of continued (prior GDNF patients) or new (prior placebo patients) exposure to GDNF for another 40 weeks. Methods: Using the infusion protocol of the parent study, all patients received GDNF without disclosing prior treatment allocations (GDNF or placebo). The primary outcome was the percentage change from baseline to Week 80 in the OFF state Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Results: All 41 parent study participants were enrolled. The primary outcome decreased by 26.7 ± 20.7% in patients on GDNF for 80 weeks (GDNF/GDNF; N = 21) and 27.6 ± 23.6% in patients on placebo for 40 weeks followed by GDNF for 40 weeks (placebo/GDNF, N = 20; least squares mean difference: 0.4%, 95% CI:-13.9, 14.6, p = 0.96). Secondary endpoints did not show significant differences between the groups at Week 80 either. Prespecified comparisons between GDNF/GDNF at Week
The goals of the Earth Biogenome Project—to sequence the genomes of all eukaryotic life on earth—are as daunting as they are ambitious. The Darwin Tree of Life Project was founded to demonstrate the credibility of these goals and to deliver at-scale genome sequences of unprecedented quality for a biogeographic region: the archipelago of islands that constitute Britain and Ireland. The Darwin Tree of Life Project is a collaboration between biodiversity organizations (museums, botanical gardens, and biodiversity institutes) and genomics institutes. Together, we have built a workflow that collects specimens from the field, robustly identifies them, performs sequencing, generates high-quality, curated assemblies, and releases these openly for the global community to use to build future science and conservation efforts.
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