scholarly journals Elevated expression of endogenous glial cell line‐derived neurotrophic factor impairs spatial memory performance and raises inhibitory tone in the hippocampus

2021 ◽  
Author(s):  
Pepin Marshall ◽  
Daniel R. Garton ◽  
Tomi Taira ◽  
Vootele Võikar ◽  
Carolina Vilenius ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Memory Performance ◽  
Elevated Expression ◽  
Inhibitory Tone

scholarly journals The Parkinson’s Disease Comprehensive Response (PDCORE): a composite approach integrating three standard outcome measures

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Matthias Luz ◽  
Alan Whone ◽  
Niccolò Bassani ◽  
Richard K Wyse ◽  
Glenn T Stebbins ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Rating Scale ◽  
Initial Development ◽  
Disease Rating ◽  
Recent Phase ◽  
Data Source

Abstract There is an increasing need for improved endpoints to assess clinical trial effects in Parkinson’s disease. We propose the Parkinson’s Disease Comprehensive Response as a novel weighted composite endpoint integrating changes measured in three established Parkinson’s outcomes, including: OFF state Movement Disorder Society Unified Parkinson’s Disease Rating Scale Motor Examination scores; Motor Experiences of Daily Living scores; and total good-quality ON time per day. The data source for the initial development of the composite described herein was a recent Phase II trial of glial cell line-derived neurotrophic factor. A wide range of clinically derived relative weights was assessed to normalize for differentially scoring base rates with each endpoint component. The Parkinson’s disease comprehensive response, in contrast to examining practically defined OFF state Unified Parkinson’s Disease Rating Scale Motor Examination scores alone, showed stability over 40 weeks in placebo patients, and all 432 analyses in this permutation exercise yielded significant differences in favour of glial cell line-derived neurotrophic factor. The findings were consistent with results obtained employing three different global statistical test methodologies and with patterns of intra-patient change. Based on our detailed analyses, we conclude it worth prospectively evaluating the clinical utility, validity and regulatory feasibility of using clinically supported final Parkinson’s disease comprehensive response formulas (for both the Unified Parkinson’s Disease Rating Scale-based and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale-based versions) in future disease-modifying Parkinson’s trials. Whilst the data source employed in the initial development of this weighted composite score is from a recent Phase II trial of glial cell line-derived neurotrophic factor, we wish to stress that the results are not described to provide post hoc evidence of the efficacy of glial cell line-derived neurotrophic factor but rather are presented to further the debate of how current regulatory approved rating scales may be combined to address some of the recognized limitations of using individual scales in isolation.

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