Evidence map›Paper›PMID 31637674›Full record

ArticleInternational journal of hematology2019

Novel lysyl oxidase inhibitors attenuate hallmarks of primary myelofibrosis in mice.

Orly Leiva, Seng Kah Ng, Shinobu Matsuura, Vipul Chitalia, Hector Lucero, Alison Findlay, Craig Turner, Wolfgang Jarolimek, Katya Ravid

Open access · greenAbstract read
In one paragraph

Article in International journal of hematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 39 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Investigational drugs in early phase trials for myelofibrosis.Expert opinion on investigational drugs · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Myofibroblast specific targeting approaches to improve fibrosis treatment.Chemical communications (Cambridge, England) · 2022
    Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. 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

9 authors at 2 institutions in 2 countries.

Orly LeivaDepartment of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany St., W-6, Boston, MA, 02118, USA.ORCID http://orcid.org/0000-0002-3006-6380
Seng Kah NgDepartment of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany St., W-6, Boston, MA, 02118, USA.
Shinobu MatsuuraDepartment of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany St., W-6, Boston, MA, 02118, USA.
Vipul ChitaliaRenal Section, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.
Hector LuceroDepartment of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany St., W-6, Boston, MA, 02118, USA.
Alison FindlayPharmaxis Ltd., 20 Rodborough Road, Frenchs Forest, NSW, Australia.
Craig TurnerPharmaxis Ltd., 20 Rodborough Road, Frenchs Forest, NSW, Australia.
Wolfgang JarolimekPharmaxis Ltd., 20 Rodborough Road, Frenchs Forest, NSW, Australia.
Katya RavidDepartment of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, 700 Albany St., W-6, Boston, MA, 02118, USA. kravid@bu.edu.
Boston University · USPanaquatic · AU

Funding

Multidisciplinary Training in Cardiovascular ResearchT32HL007224 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HAMBURG, NAOMI MIRIAM, WAINFORD, RICHARD DAVID · 1985 to 2020
$12.3M
A path to thrombosis in primary myelofibrosisR01HL136363 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAVID, KATYA · 2018 to 2021
$1.9M
The bone marrow extracellular matrix: scaffold of hematopoiesisK01OD025290 · OD · BOSTON UNIVERSITY MEDICAL CAMPUS · PI MATSUURA, SHINOBU · 2019 to 2023
$611k
NHLBI NIH HHS R01 HL136363NHLBI NIH HHS R01HL136363NHLBI NIH HHS T32 HL007224NIH HHS K01 OD025290
6 · The paper itself

Abstract

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) that usually portends a poor prognosis with limited therapeutic options available. Currently, only allogeneic stem cell transplantation is curative in those who are candidates, while administration of the JAK1/2 inhibitor ruxolitinib carries a risk of worsening cytopenia. The limited therapeutic options available highlight the need for the development of novel treatments for PMF. Lysyl oxidase (LOX), an enzyme vital for collagen cross-linking and extracellular matrix stiffening, has been found to be upregulated in PMF. Herein, we evaluate two novel LOX inhibitors, PXS-LOX_1 and PXS-LOX_2, in two animal models of PMF (GATA1low and JAK2V617F-mutated mice). Specifically, PXS-LOX_1 or vehicle was given to 15- to 16-week-old GATA1low mice via intraperitoneal injection at a dose of 15 mg/kg four times a week for 9 weeks. PXS-LOX_1 was found to significantly decrease the bone marrow fibrotic burden and megakaryocyte number compared to vehicle in both male and female GATA1low mice. Given these results, PXS-LOX_1 was then tested in 15- to 17-week-old JAK2V617F-mutated mice at a dose of 30 mg/kg four times a week for 8 weeks. Again, we observed a significant decrease in bone marrow fibrotic burden. PXS-LOX_2, a LOX inhibitor with improved oral bioavailability, was next evaluated in 15- to 17-week-old JAK2V617F-mutated mice at a dose of 5 mg/kg p.o. four times a week for 8 weeks. This inhibitor also resulted in a significant decrease in bone marrow fibrosis, albeit with a more pronounced amelioration in female mice. Taking these results together, PXS-LOX_1 and PXS-LOX_2 appear to be promising new candidates for the treatment of fibrosis in PMF.

Indexed as

AnimalsBiological AvailabilityBone Marrow NeoplasmsDisease Models, AnimalEnzyme InhibitorsFemaleMaleMicePrimary MyelofibrosisProtein-Lysine 6-OxidaseSex FactorsTreatment OutcomeEnzyme InhibitorsProtein-Lysine 6-OxidaseLysyl oxidaseMyelofibrosisMyeloproliferative neoplasm

Identifiers

PMID31637674
PMCPMC7503219
OpenAlexW2980830065

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.