NEW YORK (Reuters Health) - Inhaled antisense oligonucleotide (ASO), targeting p38-alpha mitogen-activated protein kinase (MAPK) mRNA, reduces signs of asthma in a mouse model, according to a report in the March 15th issue of the American Journal of Respiratory and Critical Care Medicine.
“p38 MAPK plays a critical role in the activation of inflammatory cells,” Dr. W.S. Fred Wong from the National University of Singapore told Reuters Health. “Respirable ASO targeted at p38-alpha represents a novel therapeutic approach to the treatment of inflammatory lung diseases, such as asthma.”
Dr. Wong and colleagues designed and synthesized a potent and selective p38-alpha-ASO and investigated its effects in a mouse asthma model.
Inhalation of p38-alpha-ASO significantly reduced ovalbumin-induced eosinophil recruitment to the lung, the authors report, and significantly attenuated ovalbumin-induced eosinophil infiltration and mucus secretion in lung tissue.
The treatment was associated with significant reductions in ovalbumin-induced IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid. Treated mice also showed significantly reduced airway hyperresponsiveness to inhaled methacholine.
Dr. Wong pointed out that “we need to develop and characterize ASO targeted at the human p38alpha MAPK mRNA sequence before it can be tested in humans.”
However, he and his colleagues conclude that the findings “support a potential role for direct aerosol administration of p38alpha MAPK ASO in the treatment of asthma and the suitability of topical ASO administration for inflammatory lung diseases using current metered dose or dry-powder inhaler technologies.”
Source: Am J Respir Crit Care Med 2005;171:571-578. [ Google search on this article ]
MeSH Headings:Mice, Inbred Strains: Specialty Chemicals and Products: Nucleic Acids, Nucleotides, and Nucleosides: Molecular Probes: Nucleic Acid Probes: RNA, Antisense: Antisense Elements (Genetics): Oligonucleotides, Antisense: Protein-Serine-Threonine Kinases: Animals, Inbred Strains: Ca(2+)-Calmodulin Dependent Protein Kinase: Laboratory Chemicals: Chemical Actions and Uses: Uses of Chemicals and Drugs: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
