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Updated: Jun 10, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Widespread decrease of type 1 cannabinoid receptor availability in Huntington disease in vivo.
Koen Van Laere1, Cindy Casteels, Isabel Dhollander
1Division of Nuclear Medicine, Leuven University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium. koen.vanlaere@uzleuven.be
Summary
Huntington disease (HD) significantly reduces type 1 cannabinoid receptor (CB1) availability in the brain, even in early stages. This in vivo finding supports the theory that mutant huntingtin impairs CB1 gene transcription.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Type 1 cannabinoid receptor (CB1) regulates synaptic transmission.
- Mutant huntingtin is hypothesized to repress CB1 transcription.
- Previous studies relied on animal and postmortem human data.
Purpose of the Study:
- To measure CB1 receptor levels in the brains of Huntington disease (HD) patients in vivo.
- To investigate the in vivo status of the endocannabinoid system in HD.
Main Methods:
- Positron Emission Tomography (PET) imaging was used.
- A novel CB1 ligand, N-[2-(3-cyano-phenyl)-3-(4-(2-(18)F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide, was administered.
- Twenty symptomatic HD patients and 14 healthy controls were studied.
Main Results:
- A significant decrease in CB1 availability was observed across the cerebrum, cerebellum, and brain stem in HD patients.
- Reductions in CB1 availability were evident even in early stages of HD.
- Disease burden (CAG repeats x age) showed an inverse correlation with CB1 availability in specific cortical regions.
Conclusions:
- The findings provide the first in vivo evidence of endocannabinoid system disruption in a human neurological disease.
- The widespread and early reduction of CB1 availability supports the hypothesis of mutant huntingtin-induced transcriptional repression.
- This study highlights the potential impact of CB1 dysregulation in the pathophysiology of Huntington disease.
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