Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma

• Published in: European respiratory review 2010-03, Vol.19 (115), p.46-54
• Main Authors: Oh, C. K, Geba, G. P, Molfino, N
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Asthma; Asthma - drug therapy; Asthma - immunology; Asthma - metabolism; Humans; interleukin-13; Interleukin-13 - immunology; Interleukin-13 - metabolism; interleukin-4; Interleukin-4 - immunology; Interleukin-4 - metabolism; monoclonal antibody; Reviews; signal transducer and activator of transcription factor-6; Signal Transduction - drug effects; Signal Transduction - immunology; STAT6 Transcription Factor - immunology; STAT6 Transcription Factor - metabolism
• ISSN: 0905-9180; 1600-0617
• DOI: 10.1183/09059180.00007609

Clinical Development, Respiratory Diseases, Allergy and Inflammation, MedImmune, LLC, Gaithersburg, MD, USA. CORRESPONDENCE: N. Molfino, MedImmune, LLC, One MedImmune Way, Gaithersburg, MD 20878, USA. E-mail: MolfinoN{at}MedImmune.com Received: November 24, 2009 Accepted January 6, 2010 ABSTRACT Asthma is a complex, persistent, inflammatory disease characterised by airway hyperresponsiveness in association with airway inflammation. Studies suggest that regular use of high-dose inhaled corticosteroids and long-acting bronchodilators or omalizumab (a humanised monoclonal antibody that binds to immunoglobulin E and is often used as next-step therapy) may not be sufficient to provide asthma control in all patients, highlighting an important unmet need. Interleukin-4, interleukin-13, and the signal transducer and activator of transcription factor-6 are key components in the development of airway inflammation, mucus production, and airway hyperresponsiveness in asthma. Biological compounds targeting these molecules may provide a new therapeutic modality for patients with uncontrolled severe asthma. The purpose of this review is to summarise current studies of compounds targeting the interleukin-4/interleukin-13 pathway and to provide a rationale for the development of such compounds for this use. KEYWORDS: Asthma, interleukin-4, interleukin-13, monoclonal antibody, signal transducer and activator of transcription factor-6