Evidence map›Paper›PMID 28159515›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2017

Local enema treatment to inhibit FOLH1/GCPII as a novel therapy for inflammatory bowel disease.

Abhijit A Date, Rana Rais, Taarika Babu, Jairo Ortiz, Pranjali Kanvinde, Ajit G Thomas, Sarah C Zimmermann, Alexandra J Gadiano, Gilad Halpert, Barbara S Slusher and 1 more

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 22% 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, 26 citations in OpenAlex.

  1. Targeting glutamate carboxypeptidase II in IBD.Advances in pharmacology (San Diego, Calif.) · 2024
    Review
  2. Article
  3. PSMA-Targeted PET Radiotracer [Clinical and experimental gastroenterology · 2023
    Article
  4. Pediatric Crohn's disease diagnosis aidFrontiers in pediatrics · 2023
    Article
  5. International journal of molecular sciences · 2022
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Spontaneous Loss-of-FunctionCrohn's & colitis 360 · 2019
    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

11 authors at 2 institutions in 1 country.

Abhijit A DateThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
Rana RaisDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Taarika BabuThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jairo OrtizThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.
Pranjali KanvindeThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA.
Ajit G ThomasDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sarah C ZimmermannDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Alexandra J GadianoDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gilad HalpertThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.
Barbara S SlusherDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Departments of Psychiatry and Behavioral Sciences, Medicine, and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: bslusher@jhmi.edu.
Laura M EnsignThe Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA. Electronic address: lensign@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Tissue pharmacology imaging and modelingU19AI113127 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MCGOWAN, IAN MICHAEL · 2014 to 2018
$20.7M
GCPII Inihibitors for the treatment of chemotherapy-induced neuropathyR01CA161056 · NCI · JOHNS HOPKINS UNIVERSITY · PI SLUSHER, BARBARA STAUCH · 2012 to 2016
$1.8M
Mucus-Penetrating Nanoparticle Containing Enemas for Ulcerative ColitisR01DK107806 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ENSIGN, LAURA, HANES, JUSTIN S. · 2016 to 2019
$1.5M
Mucus-penetrating nanoparticles for sustained microbicide deliveryR33AI079740 · NIAID · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S. · 2010 to 2012
$1.4M
Mucus Penetrating Particles for Rectal MicrobicidesR33AI094519 · NIAID · JOHNS HOPKINS UNIVERSITY · PI CONE, RICHARD, HANES, JUSTIN S. · 2013 to 2015
$1.4M
NCI NIH HHS R01 CA161056NIAID NIH HHS R33 AI079740NIAID NIH HHS R33 AI094519NIAID NIH HHS U19 AI113127NIDDK NIH HHS R01 DK107806
6 · The paper itself

Abstract

Here we evaluate the potential for local administration of a small molecule FOLH1/GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) as a novel treatment for inflammatory bowel disease (IBD). We found that FOLH1/GCPII enzyme activity was increased in the colorectal tissues of mice with TNBS-induced colitis, and confirmed that 2-PMPA inhibited FOLH1/GCPII enzyme activity ex vivo. In order to maximize local enema delivery of 2-PMPA, we studied the effect of vehicle tonicity on the absorption of 2-PMPA in the colon. Local administration of 2-PMPA in a hypotonic enema vehicle resulted in increased colorectal tissue absorption at 30min compared to 2-PMPA administered in an isotonic enema vehicle. Furthermore, local delivery of 2-PMPA in hypotonic enema vehicle resulted in prolonged drug concentrations for at least 24h with minimal systemic exposure. Finally, daily treatment with the hypotonic 2-PMPA enema ameliorated macroscopic and microscopic symptoms of IBD in the TNBS-induced colitis mouse model, indicating the potential of FOLH1/GCPII inhibitors for the local treatment of IBD.

Indexed as

EnemaAnimalsColitisColonGlutamate Carboxypeptidase IIInflammatory Bowel DiseasesIntestinal MucosaMaleMice, Inbred BALB COrganophosphorus CompoundsTrinitrobenzenesulfonic Acid2-(phosphonomethyl)pentanedioic acidGlutamate Carboxypeptidase IIOrganophosphorus CompoundsTrinitrobenzenesulfonic Acid2-PMPAColitisFolate polyglutamateHypotonicN-acetyl-aspartyl glutamateTNBS

Identifiers

PMID28159515
PMCPMC5661937
OpenAlexW2583847743

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.