DNA ANTISENSE THERAPY FOR ASTHMA IN AN ANIMAL-MODEL

Asthma is an inflammatory disease characterized by bronchial hyper-res ponsiveness that can proceed to life-threatening airway obstruction. I t is one of the most common diseases in industrialized countries, and in the United States accounts for about 1% of all healthcare costs(1). Asthma prevalence and mortality have increased dramatically over the past decade(2), and occupational asthma is predicted to be the pre-emi nent occupational lung disease in the next decade(3). Increasing evide nce suggests that adenosine, an endogenous purine that is involved in normal physiological processes, may be an important mediator of bronch ial asthma(4-15). In contrast to normal individuals, asthmatic individ uals respond to adenosine challenge with marked airway obstruction(6,7 ), and concentrations of adenosine are elevated in the bronchoalveolar lavage fluid of asthma patients(9). We performed a randomized crossov er study using the dust mite-conditioned allergic rabbit model of huma n asthma. Administration of an aerosolized phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A(1) receptor desensitize d the animals to subsequent challenge with either adenosine or dust-mi te allergen.