Evidence map›Paper›PMID 33836174›Full record

ArticleJournal of neuroscience methods2021

Modeling the mature CNS: A predictive screening platform for neurodegenerative disease drug discovery.

Kelsie Mozzoni LaBarbera, Colleen Limegrover, Courtney Rehak, Raymond Yurko, Nicholas John Izzo, Nicole Knezovich, Emily Watto, Lora Waybright, Susan M Catalano

Abstract read
In one paragraph

Article in Journal of neuroscience methods, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Long-Term Cultures of Spinal Cord Interneurons.Frontiers in cellular neuroscience · 2022
    Article
  7. 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

9 authors.

Kelsie Mozzoni LaBarberaCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Colleen LimegroverCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Courtney RehakCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Raymond YurkoCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Nicholas John IzzoCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Nicole KnezovichCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Emily WattoCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Lora WaybrightCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States.
Susan M CatalanoCognition Therapeutics Inc., Pittsburgh, PA, 15203, United States. Electronic address: scatalano@cogrx.com.

Funding

Optimization of sigma-2 receptor modulators for the treatment of cognitive dysfunctionR42AG052249 · NIA · COGNITION THERAPEUTICS, INC. · PI IZZO, NICHOLAS JOHN · 2018 to 2019
$2.1M
Target Engagement Biomarkers for Alzheimer's TherapeuticsR44AG055247 · NIA · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2016 to 2018
$2.0M
Mechanism of action of oligomer-displacing Alzheimer investigation drug, CT1812:Receptor interactions and signaling pathwaysR44AG062129 · NIA · COGNITION THERAPEUTICS, INC. · PI IZZO, NICHOLAS JOHN · 2018 to 2020
$1.8M
Structural variants of Abeta oligomer displacing small moleculesR44AG055206 · NIA · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2017 to 2019
$1.7M
Lead Optimization of receptor antagonist CT0093 for disease-modifying Alzheimer'sU01AG047059 · NIA · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2014 to 2017
$1.5M
Novel sigma-2 receptor modulators for the treatment of cognitive dysfunctionR41AG052249 · NIA · COGNITION THERAPEUTICS, INC. · PI IZZO, NICHOLAS JOHN · 2015 to 2015
$299k
New piperazines effecting Abeta oligomer displacement from neuronal receptorsR41AG052252 · NIA · COGNITION THERAPEUTICS, INC. · PI IZZO, NICHOLAS JOHN · 2016 to 2016
$224k
Small Molecule Oligomer Formation InhibitorsR43AG037337 · NIA · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2010 to 2010
$198k
Pharmacokinetic and pharmacodynamic optimization of soluble Abeta oligomer receptR43NS083175 · NINDS · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2012 to 2012
$142k
NIA NIH HHS R41 AG052249NIA NIH HHS R41 AG052252NIA NIH HHS R42 AG052249NIA NIH HHS R43 AG037337NIA NIH HHS R44 AG055206NIA NIH HHS R44 AG055247NIA NIH HHS R44 AG062129NIA NIH HHS U01 AG047059NINDS NIH HHS R43 NS083175
6 · The paper itself

Abstract

backgroundMature primary neuronal cultures are an important model of the nervous system, but limited scalability has been a major challenge in their use for drug discovery of neurodegenerative diseases. This work describes a method for improving scalability through the use of larger format microtiter plates while preserving culture quality. NEW

methodHere we describe a method and quality control procedures for growing embryonic day 18 rat hippocampal/cortical neuronal cultures in 384-well microtiter plates for three weeks in vitro.

resultsWe use these cultures in two assays measuring intracellular lipid vesicle trafficking and synapse density for routine screening of small molecule libraries. Together this culture system and screening platform have successfully identified therapeutics capable of improving cognitive function in transgenic models of Alzheimer's disease that have advanced to clinical trials, validating their translational applicability. COMPARISON WITH EXISTING

methodsOur method enables the growth of healthy, mature neurons in larger format microtiter plates than in traditional primary neuronal culturing protocols, making it ideal for drug screening and mechanism of action studies.

conclusionThe predictive capacity of this culture system and screening platform provides a method for rapidly identifying novel disease-modifying neurodegenerative therapeutics.

Indexed as

Alzheimer DiseaseNeurodegenerative DiseasesAmyloid beta-PeptidesAnimalsDrug DiscoveryNeuronsRatsAmyloid beta-PeptidesAlzheimer’s diseaseAmyloid betaAβDrug discoveryNeuronsOligomersPrimary neuronsScreening methodsTherapeutics discoveryTissue culture

Identifiers

PMID33836174
PMCPMC8217273

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.