Abstract: The present invention relates to an alternative strategy for expressing the antisense sequence of a miRNA. This system allows for continuous production of the antisense sequence and subsequently complete knockdown of the targeted miRNA.

Abstract: The invention provides a method of reducing infarct size and/or limiting, decreasing and/or inhibiting reperfusion injury and/or ameliorating heart failure in a patient comprising administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to the patient. The compound capable of inhibiting AC5 is particularly effective when administered during or after reperfusion in patients suffering from an ischemic injury.

Abstract: The invention provides methods for, and compositions effective for, treating obesity, inhibiting weight gain, treating diabetes mellitus, inhibiting atherosclerosis and treating related disorders and conditions comprising administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent. In some embodiments, the AC5 inhibiting compound is 9-?-D-arabinofuranosyladenine (AraAde). The compounds may be administered in an amount of about 1 to about 200 mg/kg/day, about 1 to about 100 mg/kg/day, about 10 to about 80 mg/kg/day, about 12 to about 40 mg/kg/day or about 15 to about 25 mg/kg/day. In some embodiments, the compound is administered orally.

Abstract: The invention relates to compositions and methods for diagnosing and treating cardiac conditions and neurodegenerative diseases using antibodies which specifically recognize and bind to the adenylyl cyclase 5 isoform in the heart and brain. These antibodies demonstrate high specificity to the AC5 isoform and do not cross react to any other AC5 isoform. The invention further relates to methods of delivery of drugs to the site of injured tissue using the antibodies of the present invention.

Abstract: The invention provides methods for, and compositions effective for, treating obesity, inhibiting weight gain, treating diabetes mellitus, inhibiting atherosclerosis and treating related disorders and conditions comprising administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent. In some embodiments, the AC5 inhibiting compound is 9-?-D-arabinofuranosyladenine (AraAde). The compounds may be administered in an amount of about 1 to about 200 mg/kg/day, about 1 to about 100 mg/kg/day, about 10 to about 80 mg/kg/day, about 12 to about 40 mg/kg/day or about 15 to about 25 mg/kg/day. In some embodiments, the compound is administered orally.

Abstract: The present invention provides novel nucleic acid and protein sequences for methods and compositions for treating, screening, and diagnosing cardiovascular disease and methods for using these genes and gene products for prevention of cardiac cell death and prevention of cardiac tissue damage resulting from ischemic events in cardiac tissue, as well as other tissue that is subject to damage resulting from an ischemic event. The genes, gene products and agents of the invention are also useful for treating other related clinical or coronary events such as angina, myocardial infarct (MI), and stroke, for monitoring the effectiveness of their treatment, and for drug development. The genes, gene products and agents of the present invention are also provided as pharmaceutical compositions for treatment of cardiovascular disease, ischemic heart disease, myocardial infarct and related conditions. Kits are also provided for the diagnosis, treatment and prognosis of cardiac diseases and related conditions.

Abstract: The present invention relates to an alternative strategy for expressing the antisense sequence of a miRNA. This system allows for continuous production of the antisense sequence and subsequently complete knockdown of the targeted miRNA.

Abstract: The invention provides a method of treating a cardiac disease by administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent, such as, for instance a ?-blocker. In some embodiments, the AC5 inhibiting compound is 9-?-D-arabinofuranosyladenine (AraAde). The compound may be administered in an amount of about 1 to about 200 mg/kg/day, about 1 to about 100 mg/kg/day, about 10 to about 80 mg/kg/day, about 12 to about 40 mg/kg/day or about 15 to about 25 mg/kg/day. In some embodiments, the compound is administered parenterally. The cardiac disease may be, for instance, myocardial infarction (MI) or heart failure (HF). The compound capable of inhibiting AC5 may be administered alone or in conjunction with one or more other active agents.

Abstract: The present invention relates to a method for identifying an agent. for modulating cell growth or survival. The method involves the identification of an agent which modulates the net ratio of nuclear-localized versus cytosolic-localized H11 kinase or mutant H11 kinase in a cell. A method for diagnosing a cancer associated with H11 kinase or Akt activation in a subject is also provided.

Abstract: The present invention provides novel nucleic acid and protein sequences for methods and compositions for treating, screening, and diagnosing cardiovascular disease and methods for using these genes and gene products for prevention of cardiac cell death and prevention of cardiac tissue damage resulting from ischemic events in cardiac tissue, as well as other tissue that is subject to damage resulting from an ischemic event. The genes, gene products and agents of the invention are also useful for treating other related clinical or coronary events such as angina, myocardial infarct (MI), and stroke, for monitoring the effectiveness of their treatment, and for drug development. The genes, gene products and agents of the present invention are also provided as pharmaceutical compositions for treatment of cardiovascular disease, ischemic heart disease, myocardial infarct and related conditions. Kits are also provided for the diagnosis, treatment and prognosis of cardiac diseases and related conditions.

Abstract: The invention relates to compositions and methods for diagnosing and treating cardiac conditions and neurodegenerative diseases using antibodies which specifically recognize and bind to the adenylyl cyclase 5 isoform in the heart and brain. These antibodies demonstrate high specificity to the AC5 isoform and do not cross react to any other AC5 isoform. The invention further relates to methods of delivery of drugs to the site of injured tissue using the antibodies of the present invention.

Abstract: The present invention relates to methods and agents for treatment, amelioration and prevention of cardiac disease, including cardiac myopathy, chronic heart failure and for management and reduction of cardiac myocyte death which may occur in response to ischemia/reperfusion or following myocardial infarction or other injury to the heart. The invention relates to methods for screening cardiotherapeutic compounds, including compounds which modulate cardiac myocyte apoptosis, particularly targeting Mst1 and the Mst1 pathway. The present invention further encompasses compounds identified by such screening methods and compositions comprising these compounds. The invention also provides methods for treatment, amelioration and prevention of cardiac disease comprising administering compounds or agents which modulate, particularly inhibit, Mst1 or the Mst1 kinase pathway, including administering a nucleic acid encoding an altered form of Mst1, particularly a dominant negative Mst1, which acts as an antagonist of Mst1.

Abstract: The present invention provides novel nucleic acid and protein sequences for methods and compositions for treating, screening, and diagnosing cardiovascular disease and methods for using these genes and gene products for prevention of cardiac cell death and prevention of cardiac tissue damage resulting from ischemic events in cardiac tissue, as well as other tissue that is subject to damage resulting from an ischemic event. The genes, gene products and agents of the invention are also useful for treating other related clinical or coronary events such as angina, myocardial infarct (MI), and stroke, for monitoring the effectiveness of their treatment, and for drug development. The genes, gene products and agents of the present invention are also provided as pharmaceutical compositions for treatment of cardiovascular disease, ischemic heart disease, myocardial infarct and related conditions. Kits are also provided for the diagnosis, treatment and prognosis of cardiac diseases and related conditions.

Abstract: The present invention relates to methods and agents for treatment, amelioration and prevention of cardiac disease, including cardiac myopathy, chronic heart failure and for management and reduction of cardiac myocyte death which may occur in response to ischemia/reperfusion or following myocardial infarction or other injury to the heart. The invention relates to methods for screening cardiotherapeutic compounds, including compounds which modulate cardiac myocyte apoptosis, particularly targeting Mst1 and the Mst1 pathway. The present invention further encompasses compounds identified by such screening methods and compositions comprising these compounds. The invention also provides methods for treatment, amelioration and prevention of cardiac disease comprising administering compounds or agents which modulate, particularly inhibit, Mst1 or the Mst1 kinase pathway, including administering a nucleic acid encoding an altered form of Mst1, particularly a dominant negative Mst1, which acts as an antagonist of Mst1.

Abstract: The present invention provides novel nucleic acid and protein sequences for methods and compositions for treating, screening, and diagnosing cardiovascular disease and methods for using these genes and gene products for prevention of cardiac cell death and prevention of cardiac tissue damage resulting from ischemic events in cardiac tissue, as well as other tissue that is subject to damage resulting from an ischemic event. The genes, gene products and agents of the invention are also useful for treating other related clinical or coronary events such as angina, myocardial infarct (MI), and stroke, for monitoring the effectiveness of their treatment, and for drug development. The genes, gene products and agents of the present invention are also provided as pharmaceutical compositions for treatment of cardiovascular disease, ischemic heart disease, myocardial infarct and related conditions. Kits are also provided for the diagnosis, treatment and prognosis of cardiac diseases and related conditions.

Abstract: The present invention relates to transgenic models of heart failure and, more particularly, to transgenic animals and methods for testing the usefulness of chemical compounds in treating or preventing heart failure. A transgenic mouse was developed wherein Gs&agr; is selectively overexpressed approximately three-fold in the heart. Although steady state adenylyl cyclase activities are not altered, both the percent of agonist high affinity &bgr;-adrenergic receptors as well as the rate of catalyst activation are increased. In addition, physiological and pathological studies revealed that chronically-facilitated sympathetic stimulation causes adverse cardiac effects.