Evidence map›Paper›PMID 30849508›Full record

ArticleNeurobiology of disease2019

Systemic peptide mediated delivery of an siRNA targeting α-syn in the CNS ameliorates the neurodegenerative process in a transgenic model of Lewy body disease.

Brian Spencer, Ivy Trinh, Edward Rockenstein, Michael Mante, Jazmin Florio, Anthony Adame, Omar M A El-Agnaf, Changyoun Kim, Eliezer Masliah, Robert A Rissman

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 2 pooled it
1.5field-weighted citation impact, top 17% 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

26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Novel Therapeutic Horizons:Biomolecules · 2024
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Assessing the Outbreak Risk of Epidemics Using Fuzzy Evidential Reasoning.Risk analysis : an official publication of the Society for Risk Analysis · 2021
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Brian SpencerDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Ivy TrinhDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Edward RockensteinDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Michael ManteDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Jazmin FlorioDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Anthony AdameDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Omar M A El-AgnafNeurological Disorders Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
Changyoun KimLaboratory of Neurogenetics National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Eliezer MasliahDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Laboratory of Neurogenetics National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Division of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Robert A RissmanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System San Diego, CA, USA. Electronic address: rrissman@ucsd.edu.
University of California San Diego · USNational Institutes of Health · USHamad bin Khalifa University · QA

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Mark W Bondi · 2019 to 2026
$34.9M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
Neuroimmune responses and therapeutics of alpha-synucleinopathies of the aging populationZIAAG000936 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2017 to 2025
$4.1M
a-synuclein clearance strategies for the treatment of Lewy body disease.R37AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2006 to 2014
$2.7M
NIA NIH HHS P30 AG062429NIA NIH HHS P50 AG005131NIA NIH HHS R01 AG018440NIA NIH HHS R37 AG018440
6 · The paper itself

Abstract

Neurodegenerative disorders of the aging population are characterized by progressive accumulation of neuronal proteins such as α-synuclein (α-syn) in Parkinson's Disease (PD) and Amyloid ß (Aß) and Tau in Alzheimer's disease (AD) for which no treatments are currently available. The ability to regulate the expression at the gene transcription level would be beneficial for reducing the accumulation of these proteins or regulating expression levels of other genes in the CNS. Short interfering RNA molecules can bind specifically to target RNAs and deliver them for degradation. This approach has shown promise therapeutically in vitro and in vivo in mouse models of PD and AD and other neurological disorders; however, delivery of the siRNA to the CNS in vivo has been achieved primarily through intra-cerebral or intra-thecal injections that may be less amenable for clinical translation; therefore, alternative approaches for delivery of siRNAs to the brain is needed. Recently, we described a small peptide from the envelope protein of the rabies virus (C2-9r) that was utilized to deliver an siRNA targeting α-syn across the blood brain barrier (BBB) following intravenous injection. This approach showed reduced expression of α-syn and neuroprotection in a toxic mouse model of PD. However, since receptor-mediated delivery is potentially saturable, each allowing the delivery of a limited number of molecules, we identified an alternative peptide for the transport of nucleotides across the BBB based on the apolipoprotein B (apoB) protein targeted to the family of low-density lipoprotein receptors (LDL-R). We used an 11-amino acid sequence from the apoB protein (ApoB

Indexed as

alpha-SynucleinAnimalsBlood-Brain BarrierBrainDisease Models, AnimalGenetic VectorsLewy Body DiseaseMiceMice, TransgenicNerve DegenerationNeuronsReceptors, LDLRNA, Small Interferingalpha-SynucleinReceptors, LDLRNA, Small InterferingApolipoprotein BBlood-brain barrierLow density lipoprotein receptorParkinson's diseaseReceptor mediated transytosissiRNAα-Synuclein

Identifiers

PMID30849508
PMCPMC6588505
OpenAlexW2918616772

What OpenQuestion holds

Textmetadata
LicenceTDM
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.