The incidence of asthma has more than doubled from 6.7 million in 1980 to 17.3 million in 1998 in the U.S., including 4.3 million children. Current therapies for asthma have serious side effects. Airway adenosine levels are increased in patients with asthma. Activation of A1 adenosine receptors produces bronchoconstriction, airway edema, and acute inflammation, leading to airflow obstruction. Endacea, Inc., a development stage biotechnology company, is developing a novel, proprietary A1 adenosine receptor (AR) antagonist, L-97-1, for asthma with a dual action: prevention of both bronchoconstriction and acute inflammation. L-97-1 is a water-soluble small molecule with high affinity and high selectivity for the human A1 AR. L-97-1 does not inhibit human phosphodiesterase enzymes and produced strong positive results in proof of concept animal asthma experiments. The goal of this STTR Phase I grant is to demonstrate: 1) efficacy in animals, in vivo, in allergic rabbit model of asthma, and 2) feasibility in humans, in vitro, in human asthmatic bronchial airway tissue for L-97-1 as a treatment for allergic asthma. These pharmacology studies and other preclinical studies will support an IND application and an STTR Phase II application for Phase I/IIa clinical trials for L-97-1 as an inhalational treatment for allergic asthma.
| Nadeem, Ahmed; Obiefuna, Peter C M; Wilson, Constance N et al. (2006) Adenosine A1 receptor antagonist versus montelukast on airway reactivity and inflammation. Eur J Pharmacol 551:116-24 |
| Obiefuna, P C M; Batra, V K; Nadeem, A et al. (2005) A novel A1 adenosine receptor antagonist, L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], reduces allergic responses to house dust mite in an allergic rabbit model of asthma. J Pharmacol Exp Ther 315:329-36 |
