The broad, long-term objective of this research is to evaluate a specific phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A1 receptor as an effective asthma therapeutic. Asthma accounts for 1% of all health care expenditures in the United States. Ten percent of adult Americans and perhaps 15% of children suffer from asthma, with about 7,000 deaths ocurring annually from asthma in the United States. This morbidity and mortality associated with asthma is increasing at an alarming rate in the United States. This morbidity and mortality associated with asthma is increasing at an alarming rate in the United States and other developed countries. Current therapeutic approaches require multidrug regimens in order to treat both the inflammatory and the bronchoconstrictor components of asthma. Furthermore, currently available drugs are not optimally effective, provide only sympotomatic relief, and have associated risks. We have developed a specific antisense oligodeoxynucleotide targeting the adenosine A1 receptor (A1AS21) which appears to have both antibronchoconstrictor and antiinflammatory effects. Our data to date conclusively show antibronchoconstrictor effects of A1AS21, while the putative antiinflammatory properties have been demonstrated only directly. If A1AS21 does indeed possess dual antibronchoconstrictor/antiinflammatory activity, it could be a potentially compelling new antiasthma agent. The present application, which is a revised application, is designed to further evaluate the antiinflammatory properties of inhaled A1AS21, to determine if it escapes the lungs in bioactive amoujnts, and to determine a minimum effective dosing schedule. POTENTIAL COMMERCIAL APPLICATIONS Asthma is a major diseas which accounts for significant morbidity, mortality, and lost productivity. The current $3 billion asthma market is growing. Currently availabe asthma drugs are suboptimal. There is clearly an unmet need for new, safer asthma drugs. The safety and efficacy profile of a A1AS21 appears promising.
| Ali, S; Leonard, S A; Kukoly, C A et al. (2001) Absorption, distribution, metabolism, and excretion of a respirable antisense oligonucleotide for asthma. Am J Respir Crit Care Med 163:989-93 |
