Evidence map›Paper›PMID 31931441›Full record

ArticleBiomaterials2020

Investigational new drug enabling angiotensin oral-delivery studies to attenuate pulmonary hypertension.

Henry Daniell, Venkata Mangu, Bakhtiyor Yakubov, Jiyoung Park, Peyman Habibi, Yao Shi, Patricia A Gonnella, Amanda Fisher, Todd Cook, Lily Zeng and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Biomaterials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

36 citing papers in PubMed, 60 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Henry DaniellDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: hdaniell@upenn.edu.
Venkata ManguDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bakhtiyor YakubovDepartment of Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Indianapolis, IN, USA.
Jiyoung ParkDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Peyman HabibiDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yao ShiDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Patricia A GonnellaDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Amanda FisherDepartment of Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Indianapolis, IN, USA.
Todd CookDepartment of Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Indianapolis, IN, USA.
Lily ZengDepartment of Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Indianapolis, IN, USA.
Steven M KawutDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tim LahmDepartment of Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Indianapolis, IN, USA; Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA; Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA.
University of Pennsylvania · USIndiana University – Purdue University Indianapolis · US

Funding

Oral immune modulatory therapy using antigens bioencapsulated in plant cellsR01HL107904 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANIELL, HENRY · 2011 to 2023
$7.5M
Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Oral Tolerance for HemophiliaR01HL133191 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2017 to 2020
$2.8M
NHLBI NIH HHS HHSN268201600011CNHLBI NIH HHS HHSN268201600014CNHLBI NIH HHS R01 HL107904NHLBI NIH HHS R01 HL109442NHLBI NIH HHS R01 HL133191
6 · The paper itself

Abstract

Pulmonary arterial hypertension (PAH) is a deadly and uncurable disease characterized by remodeling of the pulmonary vasculature and increased pulmonary artery pressure. Angiotensin Converting Enzyme 2 (ACE2) and its product, angiotensin-(1-7) [ANG-(1-7)] were expressed in lettuce chloroplasts to facilitate affordable oral drug delivery. Lyophilized lettuce cells were stable up to 28 months at ambient temperature with proper folding, assembly of CTB-ACE2/ANG-(1-7) and functionality. When the antibiotic resistance gene was removed, Ang1-7 expression was stable in subsequent generations in marker-free transplastomic lines. Oral gavage of monocrotaline-induced PAH rats resulted in dose-dependent delivery of ANG-(1-7) and ACE2 in plasma/tissues and PAH development was attenuated with decreases in right ventricular (RV) hypertrophy, RV systolic pressure, total pulmonary resistance and pulmonary artery remodeling. Such attenuation correlated well with alterations in the transcription of Ang-(1-7) receptor MAS and angiotensin II receptor AGTRI as well as IL-1β and TGF-β1. Toxicology studies showed that both male and female rats tolerated ~10-fold ACE2/ANG-(1-7) higher than efficacy dose. Plant cell wall degrading enzymes enhanced plasma levels of orally delivered protein drug bioencapsulated within plant cells. Efficient attenuation of PAH with no toxicity augurs well for clinical advancement of the first oral protein therapy to prevent/treat underlying pathology for this disease.

Indexed as

Hypertension, PulmonaryAnimalsDrugs, InvestigationalFemaleHypertrophy, Right VentricularMaleMonocrotalinePeptide FragmentsRatsRats, Sprague-DawleyDrugs, InvestigationalMonocrotalinePeptide FragmentsAffordable drug deliveryChloroplastPharmacokineticsStorageToxicology

Identifiers

PMID31931441
PMCPMC7045910
OpenAlexW2997898663

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.