Evidence map›Paper›PMID 29860333›Full record

ArticleHuman molecular genetics2018

TSPO-PET imaging using [18F]PBR06 is a potential translatable biomarker for treatment response in Huntington's disease: preclinical evidence with the p75NTR ligand LM11A-31.

Danielle A Simmons, Michelle L James, Nadia P Belichenko, Sarah Semaan, Christina Condon, Jason Kuan, Adam J Shuhendler, Zheng Miao, Frederick T Chin, Frank M Longo

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% of its field
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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. TSPO Radioligands for Neuroinflammation: An Overview.Molecules (Basel, Switzerland) · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Pharmaceutics · 2022
    Review
  10. Article
  11. Review
  12. Article
  13. TSPO imaging in animal models of brain diseases.European journal of nuclear medicine and molecular imaging · 2021
    Review
  14. Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
    Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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 at 1 institution in 1 country.

Danielle A SimmonsDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Michelle L JamesDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Nadia P BelichenkoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Sarah SemaanDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Christina CondonDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Jason KuanDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Adam J ShuhendlerDepartment of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
Zheng MiaoDepartment of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
Frederick T ChinDepartment of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, USA.
Frank M LongoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Stanford University · US

Funding

Small Molecule p75 Neurotrophin Receptor Ligand to Treat Huntington's DiseaseR21NS081089 · NINDS · STANFORD UNIVERSITY · PI LONGO, FRANK M · 2013 to 2014
$431k
NINDS NIH HHS R21 NS081089
6 · The paper itself

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder that has no cure. HD therapeutic development would benefit from a non-invasive translatable biomarker to track disease progression and treatment response. A potential biomarker is using positron emission tomography (PET) imaging with a translocator protein 18 kDa (TSPO) radiotracer to detect microglial activation, a key contributor to HD pathogenesis. The ability of TSPO-PET to identify microglial activation in HD mouse models, essential for a translatable biomarker, or therapeutic efficacy in HD patients or mice is unknown. Thus, this study assessed the feasibility of utilizing PET imaging with the TSPO tracer, [18F]PBR06, to detect activated microglia in two HD mouse models and to monitor response to treatment with LM11A-31, a p75NTR ligand known to reduce neuroinflammation in HD mice. [18F]PBR06-PET detected microglial activation in striatum, cortex and hippocampus of vehicle-treated R6/2 mice at a late disease stage and, notably, also in early and mid-stage symptomatic BACHD mice. After oral administration of LM11A-31 to R6/2 and BACHD mice, [18F]PBR06-PET discerned the reductive effects of LM11A-31 on neuroinflammation in both HD mouse models. [18F]PBR06-PET signal had a spatial distribution similar to ex vivo brain autoradiography and correlated with microglial activation markers: increased IBA-1 and TSPO immunostaining/blotting and striatal levels of cytokines IL-6 and TNFα. These results suggest that [18F]PBR06-PET is a useful surrogate marker of therapeutic efficacy in HD mice with high potential as a translatable biomarker for preclinical and clinical HD trials.

Indexed as

AnimalsCerebral CortexDisease Models, AnimalDisease ProgressionFluorodeoxyglucose F18HippocampusHumansHuntington DiseaseIsoleucineMaleMiceMicrogliaMorpholinesPositron-Emission TomographyProtein BindingReceptors, GABAFluorodeoxyglucose F18IsoleucineLM11A-31MorpholinesNgfr protein, mouseReceptors, GABAReceptors, Nerve Growth FactorTSPO protein, human

Identifiers

PMID29860333
PMCPMC6077813
OpenAlexW2807199544

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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 OpenQuestion graph.