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 costs. Asthma prevalence and mortality have increased dramatically over the past decade, and occupational asthma is predicted to be the pre-eminent occupational lung disease in the next decade. Increasing evidence suggests that adenosine, an endogenous purine that is involved in normal physiological processes, may be an important mediator of bronchial asthma. In contrast to normal individuals, asthmatic individuals respond to adenosine challenge with marked airway obstruction, and concentrations of adenosine are elevated in the bronchoalveolar lavage fluid of asthma patients. 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.
Nyce
J W
JW
Department of Molecular Pharmacology and Therapeutics, EpiGenesis Pharmaceuticals, Greenville, North Carolina 27834, USA. 104130.440@compuserve.com
Metzger
W J
WJ
D000241:Adenosine / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism; D018592:Cross-Over Studies; D016373:DNA, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008168:Lung / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000235:genetics; D012129:Respiratory Function Tests
D039741:Antigens, Dermatophagoides; D016373:DNA, Antisense; D006023:Glycoproteins; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D000241:Adenosine