The use of glucocorticoids in marmoset wasting syndrome

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Abstract

Background

Marmoset wasting syndrome (MWS) is one of the leading causes of morbidity and mortality in captive marmosets, and thus far no reliable treatment has been found. Glucocorticoids are used widely to treat inflammatory conditions of the GI tract such as human and feline inflammatory bowel disease, which, such as MWS, are histologically characterized by chronic lymphoplasmacytic inflammation in the intestines. Budesonide is a glucocorticoid with few reported side effects due to the majority of it being metabolized into inactive compounds by the liver before entering the systemic circulation.

Method

Eleven marmosets presented with antemortem signs consistent with MWS and were treated with oral prednisone or budesonide for 8 weeks.

Results

The marmosets in our study demonstrated a significant increase in both weight and albumin levels (relative to pre-treatment values) after glucocorticoid therapy.

Conclusions

Glucocorticoids are an effective therapy to ameliorate the clinical signs associated with MWS with minimal side effects.

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Most cited references 30

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Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice.

J Erichsen, Andreas Pahl, Angelika Hoffmeyer … (2013)

Although acute dextran sodium sulphate (DSS)-induced colitis in mice is frequently used as a preclinical model for testing drugs involved in inflammatory bowel disease (IBD), only limited data is available that compares the efficacy of established drug treatments and combinations employed in IBD. We have therefore compared the efficacy of aminosalicylates (mesalazine, olsalazine), corticosteroids (budesonide), thiopurines (6-thioguanine (6-TG)) and cyclosporine A (CsA) and combinations thereof as well as the EP4 agonist AGN205203 in the acute DSS-colitis model. Female BALB/c mice were challenged with 4% DSS in drinking water for 7 days to induce colitis and treated daily with different drugs/combinations orally. Disease scores (diarrhoea, bleeding, disease activity index), systemic (body weight loss, serum amyloid A levels) and colonic (myeloperoxidase activity, length and histopathology) inflammation parameters were analysed. Mesalazine, olsalazine (100mg/kg) and budesonide (0.5mg/kg) were only weakly active or even worsened colitis. 6-TG dose-dependently reduced systemic and colonic inflammation parameters with estimated ED50 values between 0.5-4 mg/kg. CsA (10, 25 and 50mg/kg) dose-dependently reduced colitis with high efficacy on systemic inflammation. A combination of CsA 25mg/kg+olsalazine 100mg/kg produced a more pronounced anti-inflammatory effect than the compounds given alone. AGN205203 (3, 10 and 30 mg/kg BID) was the most efficacious compound and almost completely inhibited colitis. 6-TG and CsA are suitable reference compounds in the DSS mouse model. CsA+olsalazine, as a combination, was more efficacious than the compounds given alone, supporting combination treatments in IBD. Copyright © 2013 Elsevier Inc. All rights reserved.

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Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study.

William J Sandborn, Simon Travis, Luigi Moro … (2012)

Budesonide is a corticosteroid with minimal systemic corticosteroid activity due to first-pass hepatic metabolism. Budesonide MMX® is a once-daily oral formulation of budesonide that extends budesonide release throughout the colon using multi-matrix system (MMX) technology.

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Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases.

H H Ali, B. Weigmann, M. F. Neurath … (2014)

The purpose of this study was to investigate the therapeutic potential of budesonide loaded nanocarriers for the treatment of inflammatory bowel disease (IBD). First, budesonide was encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles by an oil in water (O/W) emulsion technique. A second batch of the same nanoparticles was additionally coated with a pH-sensitive methyl-methacrylate-copolymer. The particle sizes of the plain and the coated PLGA were 200±10.1nm and ~240±14.7nm, respectively. As could be shown in vitro, the pH-sensitive coating prevented premature drug release at acidic pH and only releases the drug at neutral to slightly alkaline pH. The efficacy of both coated and plain nanoparticle formulations was assessed in different acute and chronic colitis mouse models, also in comparison to an aqueous solution of the drug. The dose was always the same (0.168mg/kg). It was found that delivery by coated PLGA nanoparticles alleviated the induced colitis significantly better than by plain PLGA particles, which was already more effective than treatment with the same dose of the free drug. These data further corroborate the potential of polymeric nanocarriers for targeted drug delivery to the inflamed intestinal mucosa, and that this concept can still be further improved regarding the oral route of administration by implementing pH-dependent drug release characteristics.

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Author and article information

Journal

Journal ID (nlm-ta): J Med Primatol

Journal ID (iso-abbrev): J. Med. Primatol

Journal ID (publisher-id): jmp

Title: Journal of Medical Primatology

Publisher: BlackWell Publishing Ltd (Oxford, UK )

ISSN (Print): 0047-2565

ISSN (Electronic): 1600-0684

Publication date (Print): April 2015

Publication date (Electronic): 23 January 2015

Volume: 44

Issue: 2

Pages: 53-59

Affiliations

[1 ]Research Animal Resources, Johns Hopkins University Baltimore, MD, USA

[2 ]Department of Biomedical Engineering, School of Medicine, Johns Hopkins University Baltimore, MD, USA

Author notes

Correspondence Pete Otovic, Johns Hopkins University, Research Animal Resources, 720 Rutland Ave, Ross 459, Baltimore, MD 21205, USA., Tel.: +1 410 955 3273;, fax: +1 410 502 5068;, e-mail: potovic1@ 123456jhmi.edu

Article

DOI: 10.1111/jmp.12159

PMC ID: 4415595

PubMed ID: 25614344

SO-VID: 4bd08bf6-825a-4d00-a8de-8ebb3904c2c4

License:

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

The use of glucocorticoids in marmoset wasting syndrome

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Most cited references 30

Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice.

Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study.

Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases.

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