DNA antisense therapy for asthma in an animal model

Abstract

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 asthma^4–15. In contrast to normal individuals, asthmatic individuals respond to adenosine challenge with marked airway obstruction^6,7, 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.