Literature DB >> 31446438

Vamorolone, a dissociative steroidal compound, reduces collagen antibody-induced joint damage and inflammation when administered after disease onset.

Jesse M Damsker1, Michaelyn R Cornish2, Priya Kanneboyina2, Ila Kanneboyina2, Qing Yu3, Rachel Lipson2, Aditi Phadke3, Susan M Knoblach3, Karuna Panchapakesan3, Melissa Morales4, Alyson A Fiorillo3, Terence Partridge3, Kanneboyina Nagaraju5,6,7.   

Abstract

OBJECTIVE AND
DESIGN: The objective of this study was to assess the effect of vamorolone, a first-in-class dissociative steroidal compound, to inhibit inflammation when administered after disease onset in the murine collagen antibody-induced arthritis model of arthritis. ANIMALS: 84 DBA1/J mice were used in this study (n = 12 per treatment group). TREATMENT: Vamorolone or prednisolone was administered orally after disease onset for a duration of 7 days.
METHODS: Disease score and bone erosion were assessed using previously described scoring systems. Cytokines were measured in joints via immunoassay, and joint cathepsin B activity (marker of inflammation) was assessed using optical imaging of joints on live mice.
RESULTS: We found that vamorolone treatment led to a reduction of several disease parameters including disease score, joint inflammation, and the presence of pro-inflammatory mediators to a degree similar of that observed with prednisolone treatment. More importantly, histopathological analysis of affected joints showed that vamorolone treatment significantly reduced the degree of bone erosion while this bone-sparing property was not observed with prednisolone treatment at any of the tested doses.
CONCLUSIONS: While many intervention regimens in other studies are administered prior to disease onset in animal models, the current study involves delivery of the potential therapeutic after disease onset. Based on the findings, vamorolone may offer an efficacious, yet safer alternative to conventional steroidal compounds in the treatment of rheumatoid arthritis and other inflammatory diseases.

Entities:  

Keywords:  Autoimmunity; Glucocorticoids; Inflammation; Rheumatoid arthritis

Mesh:

Substances:

Year:  2019        PMID: 31446438      PMCID: PMC6814568          DOI: 10.1007/s00011-019-01279-z

Source DB:  PubMed          Journal:  Inflamm Res        ISSN: 1023-3830            Impact factor:   4.575


  35 in total

1.  Quantitative analysis of cytokine gene expression in rheumatoid arthritis.

Authors:  G S Firestein; J M Alvaro-Gracia; R Maki; J M Alvaro-Garcia
Journal:  J Immunol       Date:  1990-05-01       Impact factor: 5.422

2.  Interleukin-4 can be a key positive regulator of inflammatory arthritis.

Authors:  Koichiro Ohmura; Linh T Nguyen; Richard M Locksley; Diane Mathis; Christophe Benoist
Journal:  Arthritis Rheum       Date:  2005-06

3.  Collagen antibody-induced arthritis.

Authors:  Levon M Khachigian
Journal:  Nat Protoc       Date:  2006       Impact factor: 13.491

Review 4.  Developing an effective treatment algorithm for rheumatoid arthritis.

Authors:  Edward C Keystone; Josef Smolen; Piet van Riel
Journal:  Rheumatology (Oxford)       Date:  2012-07       Impact factor: 7.580

5.  Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment.

Authors:  I Rioja; K A Bush; J B Buckton; M C Dickson; P F Life
Journal:  Clin Exp Immunol       Date:  2004-07       Impact factor: 4.330

6.  Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis.

Authors:  B Tong; B Wan; Z Wei; T Wang; P Zhao; Y Dou; Z Lv; Y Xia; Y Dai
Journal:  Clin Exp Immunol       Date:  2014-09       Impact factor: 4.330

7.  Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

Authors: 
Journal:  Lancet       Date:  2016-10-08       Impact factor: 79.321

8.  VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects.

Authors:  Christopher R Heier; Jesse M Damsker; Qing Yu; Blythe C Dillingham; Tony Huynh; Jack H Van der Meulen; Arpana Sali; Brittany K Miller; Aditi Phadke; Luana Scheffer; James Quinn; Kathleen Tatem; Sarah Jordan; Sherry Dadgar; Olga C Rodriguez; Chris Albanese; Michael Calhoun; Heather Gordish-Dressman; Jyoti K Jaiswal; Edward M Connor; John M McCall; Eric P Hoffman; Erica K M Reeves; Kanneboyina Nagaraju
Journal:  EMBO Mol Med       Date:  2013-09-09       Impact factor: 12.137

9.  Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes.

Authors:  Eric P Hoffman; Valerie Riddle; Maxime A Siegler; Daniel Dickerson; Miroslav Backonja; William G Kramer; Kanneboyina Nagaraju; Heather Gordish-Dressman; Jesse M Damsker; John M McCall
Journal:  Steroids       Date:  2018-03-08       Impact factor: 2.668

10.  VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice.

Authors:  Jesse M Damsker; Blythe C Dillingham; Mary C Rose; Molly A Balsley; Christopher R Heier; Alan M Watson; Erik J Stemmy; Roslyn A Jurjus; Tony Huynh; Kathleen Tatem; Kitipong Uaesoontrachoon; Dana M Berry; Angela S Benton; Robert J Freishtat; Eric P Hoffman; John M McCall; Heather Gordish-Dressman; Stephanie L Constant; Erica K M Reeves; Kanneboyina Nagaraju
Journal:  PLoS One       Date:  2013-05-07       Impact factor: 3.240

View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.