Evidence map›Paper›PMID 34738197›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2021

SPG302 Reverses Synaptic and Cognitive Deficits Without Altering Amyloid or Tau Pathology in a Transgenic Model of Alzheimer's Disease.

Laura Trujillo-Estrada, Peter W Vanderklish, Marie Minh Thu Nguyen, Run Rong Kuang, Caroline Nguyen, Eric Huynh, Celia da Cunha, Dominic Ibarra Javonillo, Stefania Forner, Alessandra C Martini and 4 more

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

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 27% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026
    Review
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  5. Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026
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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

14 authors at 2 institutions in 2 countries.

Laura Trujillo-EstradaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Peter W Vanderklish *Spinogenix Inc, 10210 Campus Point Drive, Suite 150, San Diego, CA, 92121, USA. peter@spinogenix.com.
Marie Minh Thu NguyenInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Run Rong KuangInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Caroline NguyenInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Eric HuynhInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Celia da CunhaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Dominic Ibarra JavonilloInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Stefania FornerInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Alessandra C MartiniInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Stella T SarrafSpinogenix Inc, 10210 Campus Point Drive, Suite 150, San Diego, CA, 92121, USA.
Vincent F Simmon *Spinogenix Inc, 10210 Campus Point Drive, Suite 150, San Diego, CA, 92121, USA. vince@spinogenix.com.
David Baglietto-Vargas *Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA. d.baglietto@uma.es.
Frank M LaFerla *Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA. laferla@uci.edu.
University of California, Irvine · USBiomedical Research Networking Center on Neurodegenerative Diseases · ES

Funding

Novel small molecules that target Alzheimer's disease by increasing spinogenesis and decreasing A-beta toxicityR43AG058278 · NIA · SPINOGENIX, INC. · PI SIMMON, VINCENT F. · 2018 to 2018
$315k
NIA NIH HHS R43 AG058278
6 · The paper itself

Abstract

Alzheimer's disease (AD) is conceptualized as a synaptic failure disorder in which loss of glutamatergic synapses is a major driver of cognitive decline. Thus, novel therapeutic strategies aimed at regenerating synapses may represent a promising approach to mitigate cognitive deficits in AD patients. At present, no disease-modifying drugs exist for AD, and approved therapies are palliative at best, lacking in the ability to reverse the synaptic failure. Here, we tested the efficacy of a novel synaptogenic small molecule, SPG302 - a 3rd-generation benzothiazole derivative that increases the density of axospinous glutamatergic synapses - in 3xTg-AD mice. Daily dosing of 3xTg-AD mice with SPG302 at 3 and 30 mg/kg (i.p.) for 4 weeks restored hippocampal synaptic density and improved cognitive function in hippocampal-dependent tasks. Mushroom and stubby spine profiles were increased by SPG302, and associated with enhanced expression of key postsynaptic proteins - including postsynaptic density protein 95 (PSD95), drebrin, and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) - and increased colocalization of PSD95 with synaptophysin. Notably, SPG302 proved efficacious in this model without modifying Aβ and tau pathology. Thus, our study provides preclinical support for the idea that compounds capable of restoring synaptic density offer a viable strategy to reverse cognitive decline in AD.

Indexed as

Alzheimer DiseaseCognition DisordersCognitive DysfunctionAmyloid beta-PeptidesAnimalsCognitionDisease Models, AnimalHippocampusHumansMiceMice, TransgenicSynapsestau ProteinsAmyloid beta-Peptidestau Proteins3xTg-AD miceAlzheimer’s diseaseDendritic spinesSPG302Synaptic deficitsSynaptic markers

Identifiers

PMID34738197
PMCPMC8804111
OpenAlexW3210724044

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.