{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:21:10Z","timestamp":1793931670753,"version":"4.8.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The drug product TPI ASM8 contains two modified phosphorothioate antisense oligonucleotides designed to inhibit allergic inflammation by down-regulating human CCR3 and the common beta chain (\u03b2c) of IL-3, IL-5, and granulocyte-macrophage colony\u2013stimulating factor receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study examined the effects of inhaled TPI ASM8 on sputum cellular influx, CCR3 and \u03b2c mRNA and protein levels, and the airway physiologic response after inhaled allergen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventeen subjects with mild atopic asthma were randomized in a crossover study to inhale 1,500 \u03bcg TPI ASM8 or placebo by nebulizer, once daily for 4 days. On Day 3, subjects underwent allergen inhalation challenge. Sputum samples were collected before and after allergen. CCR3 and \u03b2c protein levels were measured by flow cytometry, mRNA was measured using real-time quantitative polymerase chain reaction, and the FEV1 was measured over 7 hours after challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Compared with placebo, TPI ASM8 inhibited sputum eosinophil influx by 46% (P = 0.02) and blunted the increase in total cells (63%) after allergen challenge. TPI ASM8 significantly reduced the early asthmatic response (P = 0.04) with a trend for the late asthmatic response (P = 0.08). The allergen-induced (Day 2 to Day 3) levels of \u03b2c mRNA and CCR3 mRNA in sputum-derived cells were inhibited by TPI ASM8 (P = 0.039 and P = 0.054, respectively), with no significant effects on the cell surface protein expression of CCR3 and \u03b2c (P &amp;gt; 0.05). No serious adverse events were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TPI ASM8 attenuates the allergen-induced increase in target gene mRNA and airway responses in subjects with mild asthma.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT00264966).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200708-1251oc","type":"journal-article","created":{"date-parts":[[2008,1,31]],"date-time":"2008-01-31T21:50:43Z","timestamp":1201816243000},"page":"952-958","source":"Crossref","is-referenced-by-count":129,"title":["Antisense Therapy against CCR3 and the Common Beta Chain Attenuates Allergen-induced Eosinophilic Responses"],"prefix":"10.1093","volume":"177","author":[{"given":"Gail M.","family":"Gauvreau","sequence":"first","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis Philippe","family":"Boulet","sequence":"additional","affiliation":[{"name":"Institut de Cardiologie et de Pneumologie de l\u2019Universit\u00e9 Laval, H\u00f4pital Laval, Quebec City, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald W.","family":"Cockcroft","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Baatjes","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Cote","sequence":"additional","affiliation":[{"name":"Institut de Cardiologie et de Pneumologie de l\u2019Universit\u00e9 Laval, H\u00f4pital Laval, Quebec City, Quebec, 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