Evidence map›Paper›PMID 33798648›Full record

ReviewDrug discovery today2021

Nipping disease in the bud: nSMase2 inhibitors as therapeutics in extracellular vesicle-mediated diseases.

Carolyn Tallon, Kristen R Hollinger, Arindom Pal, Benjamin J Bell, Rana Rais, Takashi Tsukamoto, Kenneth W Witwer, Norman J Haughey, Barbara S Slusher

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Drug discovery today, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing 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

44 citing papers in PubMed.

  1. Review
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  18. Novel Pyrazolo[1,5-ACS medicinal chemistry letters · 2025
    Article
  19. Article
  20. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
    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.

Carolyn TallonJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kristen R HollingerJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Arindom PalJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Benjamin J BellJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rana RaisJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Takashi TsukamotoJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kenneth W WitwerDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Norman J HaugheyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Barbara S SlusherJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: bslusher@jhmi.edu.

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
Next-generation extracellular vesicle biologics to target central nervous system and peripheral reservoirs of HIVR01AI144997 · NIAID · JOHNS HOPKINS UNIVERSITY · PI RAMRATNAM, BHARAT, WITWER, KENNETH W · 2019 to 2023
$4.0M
Extracellular Vesicle and Extracellular RNA Biomarkers of HIV-1 Central Nervous System Pathogenesis and Cigarette UseR01DA047807 · NIDA · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2018 to 2022
$3.7M
Translational Research in Neuro-AIDS and Mental HealthR25MH080661 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MCARTHUR, JUSTIN CHARLES. · 2007 to 2019
$2.9M
Regulation of Exosome Secretion as a novel therapeutic approach for Alzheimer's DiseaseR01AG059799 · NIA · JOHNS HOPKINS UNIVERSITY · PI SLUSHER, BARBARA STAUCH, TSUKAMOTO, TAKASHI · 2018 to 2022
$2.4M
Dendrimer-conjugated nSMase2 inhibitor as a novel therapeutic approach for Alzheimer's DiseaseR01AG063831 · NIA · JOHNS HOPKINS UNIVERSITY · PI RAIS, RANA, RANGARAMANUJAM, KANNAN · 2020 to 2024
$2.3M
Novel Approaches to Capture, Sorting, and Characterization of CNS-Origin Extracellular VesiclesR33MH118164 · NIMH · JOHNS HOPKINS UNIVERSITY · PI MACHAIRAKI, VASILIKI, WITWER, KENNETH W · 2020 to 2022
$2.2M
Novel Separation Methods for exRNA Carriers: Extracellular Vesicles, Lipoprotein Particles, and Protein AggregatesUH3CA241694 · NCI · JOHNS HOPKINS UNIVERSITY · PI WITWER, KENNETH W · 2021 to 2022
$1.1M
NCI NIH HHS UH3 CA241694NIAID NIH HHS R01 AI144997NIA NIH HHS R01 AG059799NIA NIH HHS R01 AG063831NIDA NIH HHS R01 DA047807NIMH NIH HHS P30 MH075673NIMH NIH HHS R25 MH080661NIMH NIH HHS R33 MH118164
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are indispensable mediators of intercellular communication, but they can also assume a nefarious role by ferrying pathological cargo that contributes to neurological, oncological, inflammatory, and infectious diseases. The canonical pathway for generating EVs involves the endosomal sorting complexes required for transport (ESCRT) machinery, but an alternative pathway is induced by the enrichment of lipid membrane ceramides generated by neutral sphingomyelinase 2 (nSMase2). Inhibition of nSMase2 has become an attractive therapeutic strategy for inhibiting EV biogenesis, and a growing number of small-molecule nSMase2 inhibitors have shown promising therapeutic activity in preclinical disease models. This review outlines the function of EVs, their potential role in disease, the discovery and efficacy of nSMase2 inhibitors, and the path to translate these findings into therapeutics.

Indexed as

Extracellular VesiclesAnimalsDrug ResistanceHumansImmunotherapyNeoplasmsNeurodegenerative DiseasesSphingomyelin PhosphodiesteraseSMPD3 protein, humanSphingomyelin PhosphodiesteraseBiomarkerCell communicationCeramideDrug discoveryExtracellular vesicleSphingomyelinase

Identifiers

PMID33798648
PMCPMC8364476

What Socratic holds

Textmetadata
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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 Socratic graph.