Abstract: Presented are mechanism based compositions and methods for treatment of SCD and SCD associated symptoms and disorders, particularly increased RBC sickling, HbS polymerization, hemolysis, tissue congestion and disruption and organ damage or failure in a mammal. The disclosed methods feature the identification of the heretofore unknown role of adenosine levels and signaling in the development of SCD and SCD associated symptoms and disorders. This discovery has lead to the identification of compositions for use as therapies for SCD and SCD associated disorders and symptoms in a mammal.

Abstract: We disclose a method of treating priapism in a mammal by administering to the mammal a composition containing an effective amount of an inhibitor of adenosine signaling and a pharmaceutically-acceptable carrier, wherein the inhibitor of adenosine signaling has at least one activity selected from the group consisting of decreasing adenosine levels in the mammal, inhibiting adenosine receptor activity in the mammal, and inhibiting signaling pathways downstream of an adenosine receptor in the mammal.

Abstract: The present invention relates to the production of adenosine deaminase (ADA) deficient mice and the use of such mice as an animal model for dysfunctions associated with elevated adenosine levels. Also, provided by the present invention are methods of treating dysfunctions associated with elevated adenosine levels and methods of screening compounds for pharmaceutical activity in the treatment of dysfunctions associated with elevated adenosine levels.

Abstract: The present invention relates to the production of adenosine deaminase (ADA) deficient mice and the use of such mice as an animal model for dysfunctions associated with elevated adenosine levels. Also, provided by the present invention are methods of treating dysfunctions associated with elevated adenosine levels and methods of screening compounds for pharmaceutical activity in the treatment of dysfunctions associated with elevated adenosine levels.

Abstract: Disclosed are cultured mouse cells with amplified adenosine deaminase genes which greatly overproduce adenosine deaminase. The cells were isolated by growth in media containing alanosine, uridine, and a cytotoxic concentration of adenosine. Maximum enhancement of adenosine deaminase activity was achieved by also adding deoxycoformycin to the media and then serially increasing the deoxycoformycin concentration at 4 to 6 week intervals. Also disclosed is a cDNA homologous to mouse adenosine deaminase mRNA. The cDNA was produced by synthesis against RNA extracted from the cells containing amplified adenosine deaminase genes and then inserted into a bacterial plasmid. Multiple copies of the cDNA were produced by replication of the bacteria into which the plasmids were inserted.