DNA antisense therapy for asthma in an animal model

Asthma is an inflammatory disease characterized by bronchial hyper-responsiveness that can proceed to life-threatening airway obstruction. It is one of the most common diseases in industrialized countries, and in the United States accounts for about 1% of all healthcare costs1. Asthma prevalence and mortality have increased dramatically over the past decade2, and occupational asthma is predicted to be the pre-eminent occupational lung disease in the next decade3. Increasing evidence suggests that adenosine, an endogenous purine that is involved in normal physiological processes, may be an important mediator of bronchial asthma4–15. In contrast to normal individuals, asthmatic individuals respond to adenosine challenge with marked airway obstruction6,7, and concentrations of adenosine are elevated in the bronchoalveolar lavage fluid of asthma patients9. We performed a randomized crossover study using the dust mite-conditioned allergic rabbit model of human asthma. Administration of an aerosolized phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A1 receptor desensitized the animals to subsequent challenge with either adenosine or dust-mite allergen.