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Investigation in the cannabigerol derivative VCE-003.2 as a disease- modifying agent in a mouse model of experimental synucleinopathy

ABSTRACT: Investigation in the cannabigerol derivative VCE-003.2 as a disease- modifying agent in a mouse model of experimental synucleinopathy

PROVIDER: PRJEB72409 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR12644959.fastq.gz	Fastqsanger.gz
	ERR12644960.fastq.gz	Fastqsanger.gz
	ERR12644961.fastq.gz	Fastqsanger.gz
	ERR12644962.fastq.gz	Fastqsanger.gz
	ERR12644963.fastq.gz	Fastqsanger.gz

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Project description:BackgroundDopamine transporter single photon-emission computed tomography (DAT-SPECT) is the strongest risk factor for phenoconversion in patients with idiopathic rapid eye movement (REM)-sleep behavior disorder (iRBD). However, it might be used as a second-line stratification tool in clinical trials, because it is expensive and mini-invasive.ObjectiveAim of the study is to investigate whether other cost-effective and non-invasive biomarkers may be proposed as first-line stratification tools.MethodsForty-seven consecutive iRBD patients (68.53 ± 7.16 years, 40 males) underwent baseline clinical and neuropsychological assessment, olfaction test, resting electroencephalogram (EEG), and DAT-SPECT. All patients underwent 6 month-based clinical follow-up to investigate the emergence of parkinsonism and/or dementia. Survival analysis and Cox regression were used to estimate conversion risk.ResultsSeventeen patients developed an overt synucleinopathy (eight Parkinsonism and nine dementia) 32.8 ± 22 months after diagnosis. The strongest risk factors were putamen specific to non-displaceable binding ratio (SBR) (hazard ratio [HR], 7.3), attention/working memory cognitive function (NPS-AT/WM) (HR, 5.9), EEG occipital mean frequency (HR, 2.7) and clinical motor assessment (HR, 2.3). On multivariate Cox-regression analysis, only putamen SBR and NPS-AT/WM significantly contributed to the model (HR, 6.2, 95% confidence interval [CI], 1.9-19.8). At post-hoc analysis, the trail-making test B (TMT-B) was the single most efficient first-line stratification tool that allowed to reduce the number of eligible subjects to 76.6% (sensitivity 1, specificity 0.37). Combining TMT-B and DAT-SPECT further reduced the sample to 66% (sensitivity 0.88, specificity 0.47).ConclusionThe TMT-B seems to be a cost-effective and efficient first-line screening tool, to be used to select patients that deserve DAT-SPECT as second-line screening tool for disease-modifying clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Investigation in the cannabigerol derivative VCE-003.2 as a disease- modifying agent in a mouse model of experimental synucleinopathy

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