Evidence mapPaperPMID 39487447Full record

ArticleBehavioral and brain functions : BBF2024

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

Sonia Burgaz, Elisa Navarro, Santiago Rodríguez-Carreiro, Carmen Navarrete, Martin Garrido-Rodríguez, Isabel Lastres-Becker, Julia Chocarro, José L Lanciego, Eduardo Muñoz, Javier Fernández-Ruiz

Abstract read
In one paragraph

Article in Behavioral and brain functions : BBF, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Sonia BurgazDepartamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.
Elisa NavarroDepartamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.
Santiago Rodríguez-CarreiroDepartamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.
Carmen NavarreteEmerald Health Pharmaceuticals, San Diego, USA.
Martin Garrido-RodríguezInstituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
Isabel Lastres-BeckerCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Julia ChocarroCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
José L LanciegoCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Eduardo MuñozInstituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain. fi1muble@uco.es.ORCID http://orcid.org/0000-0001-8478-5842
Javier Fernández-RuizDepartamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain. jjfr@med.ucm.es.ORCID http://orcid.org/0000-0002-4490-0604

Funding

Instituto de Salud Carlos III CB06/05/0089Ministerio de Ciencia e Innovación PID2021-128906OB-I00Ministerio de Ciencia e Innovación PID2022-137065OB-I00Ministerio de Ciencia e Innovación PID2022-139936OA-I00
6 · The paper itself

Abstract

backgroundThe cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis.

methodsTo this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc.

resultsOral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling.

conclusionOur study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.

Indexed as

alpha-SynucleinDisease Models, AnimalSynucleinopathiesAnimalsCannabinoidsMaleMiceMice, Inbred C57BLNeuroprotective AgentsParkinsonian DisordersPars CompactaQuinonesalpha-SynucleinCannabinoidsNeuroprotective AgentsQuinonesVCE-003alpha-synucleinCannabinoidsParkinson’s diseasePPAR-γVCE-003.2

Identifiers

PMID39487447
PMCPMC11531178

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.