ADENOSINE A1 RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE

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. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 418 --PROJECT NUMBER......1 R43 HL57724-01 INVESTIGATOR NAME/ADDRESS FY 97 WALKER, STEVE D IRG/INTRAMURAL UNIT..ZRG3 ANALASE LLC AWARD AMOUNT......... $99,792 4760 WALNUT STREET, SUITE 102 BOULDER, COLORADO 80301-2561 PERFORMING ORGANIZATION: ANALASE LLC TITLE MAINSTREAM ANESTHETIC AGENT SENSOR ABSTRACT: There currently is no mainstream anesthetic agent sensor because existing technologies are too large and heavy to be mounted on a patient's airway. Our aim is to develop the next-generation, compact, high reliability, mid- IR spectrometer which will he able to quickly and unambiguously identify the presence and concentration of a large range of anesthetic gases. The spectrometer would be compact enough to be mounted in the patient's airway, close enough to provide a breath-by-breath response to changing gas composition. Currently, the design and manufacture of a sufficiently compact spectrometer is hindered by the lack of a small, reliable component needed to chop (rapidly turn ON and OFF) the IR (infrared) beam used in the spectrometer. Mid-IR detectors require a chopped light source. Current electro-mechanical choppers are too large, suffer from performance degrading jitter, generate unwanted vibrations, and are less reliable than the electronic components used in spectrometers. We propose to use a compact, inexpensive, electro-optic chopper (non-mechanical, no moving parts) using ferroelectric liquid crystal technology. In addition to medical applications this spectrometer will also be valuable in spectrometers intended for applications such as environmental monitoring and automobile emissions testing.