SELECTED ARTICLES FROM THE RECENT LITERATURE 2008

5/12/2008

Antisense Therapy for Asthma

Summary
The authors employed a drug called TPI ASM8 which contains two modified phosphorothioate antisense oligonucleotides designed to inhibit allergic inflammation via the downregulation of CCR3 and the common beta chain of IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor receptors.

Seventeen subjects with mild allergic asthma were evaluated. The study was conducted via a randomized crossover protocol. Subjects inhaled 1500 mcg of TPI ASM8 or placebo once daily for four days. On day three, they underwent allergen inhalation challenge. Sputum samples and lung functions were assayed. TPI ASM8 significantly inhibited eosinophil influx and blunted the total cell count. It also significantly reduced the early asthmatic response and showed a trend for same in the late asthmatic response. It also reduced levels of the common beta chain messenger RNA and CCR3 messenger RNA in sputum cells. However, there was no significant effect on the cell surface protein expression of the common beta chain and CCR3. In addition, although the sputum eosinophils where diminished at seven hours, they were not significantly decreased at 24 hours after allergen challenge. Thus, antisense therapy was able to decrease some manifestations of inflammation, but further studies are needed to assess the clinical importance of these findings.

Reference
Gauvreau GM, et al. Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. American Journal of Respiratory and Critical Care Medicine 2008; 177:952-958.

 

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