Calcium/Calmodulin-Dependent Protein Kinase Kinase as a Control Point for Cardiac Hypertrophy

A composition for modulating a cardiac hypertrophy comprising an amount of a Calmodulin kinase kinase modulator sufficient to change the activity of the Calmodulin kinase kinase.

A pharmaceutical composition for treating a cardiac hypertrophy comprising a pharmaceutically effective amount of a Calmodulin kinase kinase inhibitor sufficient to treat a patient suspected of having cardiac hypertrophy.

A method of treating a modulating muscle mass comprising:

• administering to a patient in need thereof a composition comprising a Calmodulin kinase kinase inhibitor in a pharmaceutically acceptable carrier, in an amount insufficient to treat the cardiac hypertrophy.

A method for treating or preventing hypertrophic cardiomyopathy in a mammal, the method comprising administering a Calmodulin kinase kinase inhibitor to the mammal, wherein the Calmodulin kinase kinase inhibitor is administered in an amount effective to treat or prevent heart failure in the mammal.

A method of treating a disease in a mammal resulting from deficiencies of cardiac output comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a Calmodulin kinase kinase inhibitor.

A method of modulating muscle mass comprising administering to a patient in need of an increase or a decrease in muscle mass an amount of a Calmodulin kinase kinase modulator sufficient to alter the muscle mass.

A method for diagnosing hypertrophic cardiomyopathy in a mammal, the method comprising measuring the Calmodulin kinase kinase activity from the mammal suspected of having the hypertrophic cardiomyopathy to the levels of kinase activity in a mammal known to have a normal cardiac function.

A method for screening compounds for the ability to prevent or treat the manifestations of heart failure, comprising:

• contacting a Calmodulin kinase kinase to one or more candidate substances;
• and
• measuring the effect of the candidate substance on the kinase activity of the Calmodulin kinase kinase, wherein a candidate substance identified thereby is subsequently tested for improvement in the physiologic function of the heart of the mouse, thereby identifying a compound as therapeutic.

A diet for supporting a patient with cardiac hypertrophy comprising a nutritionally effective amount of a Calmodulin kinase kinase modulator to reduce the symptoms associated with cardiac hypertrophy and decreases muscle mass.

A food composition comprising:

• a mixture of ingredients selected to make one or more snacks, soups, salads, cakes, cookies, crackers, breads, ice creams, yogurts, puddings, custards, baby foods, medicinal foods, sports bars, breakfast cereals and beverages;
• and
• a Calmodulin kinase kinase inhibitor comprising a concentration of between about 0.5% to about 5.0% of the composition.

A nutritional supplement comprising a nutritionally effective amount of a Calmodulin kinase kinase modulator sufficient to modulate muscle size.

A transgenic mouse displaying manifestations of cardiac hypertrophy selected from the group consisting of:

• shortness of breath, angina, palpitations, lightheadedness, fatigue, syncope, dyspnea, elevated pressure in the left ventricle and left atrium and combinations thereof relative to a control mouse, wherein the genome of the mouse comprises a promoter operably linked to a nucleotide sequence encoding a Calmodulin kinase kinase, and a Calmodulin kinase kinase in its cardiac tissue at a level that is at least 3-fold higher than in cardiac tissue of a control mouse.