Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.
Abstract: Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown promising results. Objective: The aim of this study was to evaluate the clinical and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo-controlled, prospective, randomized clinical trial and to verify a sustained effect post-treatment. Methods: Twenty-four RAO-affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post-treatment (III). Results: At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage, and an increase in arterial oxygen pressure. Conclusions: Administration of a GNP-bound CpG-ODN formulation caused a potent and persistent effect on allergic and inflammatory-induced clinical variables in RAO-affected horses. This treatment, therefore, provides an innovative, promising, and well-tolerated strategy beyond conventional symptomatic long-term therapy and could serve as a model for asthma treatment in humans.
Copyright © 2015 by the American College of Veterinary Internal Medicine.
Publication Date: 2015-01-27 PubMed ID: 25619520PubMed Central: PMC4858074DOI: 10.1111/jvim.12524Google Scholar: Lookup
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- Clinical Trial
- Phase I
- Clinical Trial
- Phase II
- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses the use of Gelatin Nanoparticles (GNP) loaded with Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) to rebalance the immune response in horses affected by Recurrent Airway Obstruction (RAO). The preliminary results show reduced respiratory symptoms in the horses, promising a potential new treatment approach for RAO and, possibly, human asthma.
Introduction and Objective
- The paper explores the use of CpG-ODN, substances known to stimulate the Th1-pathway of the immune system, encapsulated in Gelatin Nanoparticles (GNP). This approach aims to shift the immune response from a pro-allergic Th2-line (which typically characterizes RAO) to a Th1-pathway (less associated with allergic reactions).
- The goal of the study was to evaluate the clinical and immunological effects of the GNP-bound CpG-ODN on horses suffering from RAO. The researchers also aimed to verify whether these effects were sustained over time.
Methods
- Twenty-four RAO-affected horses participated in this double-blinded, placebo-controlled, randomized clinical trial.
- The horses received an inhalation of GNP-bound CpG-ODN every two days for five consecutive days. Their clinical and immunological status was evaluated before the treatment (I), immediately afterwards (II), and four weeks after the treatment ended (III).
Results
- The study found significant improvements in treated horses at times I and II, with a decrease in respiratory effort, nasal discharge, tracheal secretion, viscosity, AaDO2 (which measures oxygen diffusion efficiency), and neutrophil percentage (indicating decreased inflammation).
- An increase in arterial oxygen pressure was also observed, indicating better oxygen supply.
Conclusions
- The use of GNP-bound CpG-ODN has shown potent and lasting effects on RAO symptoms, making it a potentially promising and novel treatment strategy.
- Due to the asthma-like nature of RAO, this research could inspire groundbreaking strategies for human asthma treatment as well.
Cite This Article
APA
Klier J, Lehmann B, Fuchs S, Reese S, Hirschmann A, Coester C, Winter G, Gehlen H.
(2015).
Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.
J Vet Intern Med, 29(1), 286-293.
https://doi.org/10.1111/jvim.12524 Publication
Researcher Affiliations
- Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig Maximilians University, Munich, Germany.
MeSH Terms
- Animals
- Auscultation
- Female
- Horse Diseases / drug therapy
- Horses
- Lung / pathology
- Lung Diseases, Obstructive / drug therapy
- Lung Diseases, Obstructive / veterinary
- Male
- Mucus
- Nanoparticles / adverse effects
- Nanoparticles / therapeutic use
- Oligodeoxyribonucleotides / adverse effects
- Oligodeoxyribonucleotides / therapeutic use
- Oxygen / blood
- Partial Pressure
- Respiration / drug effects
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Citations
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