Treatment of heart disease by inhibtion of the action of muscle A-kinase anchoring protein (mAKAP)
The present invention provides a method of protecting the heart from damage, by administering to a patient at risk of such damage, a pharmaceutically effective amount of a composition which inhibits the interaction of RSK3 and mAKAPβ, or the expression or activity of one or both of those molecules. This composition is preferably in the form of an siRNA construct, more preferably an shRNA construct, which inhibits the expression of mAKAPβ.
1. A composition comprising a vector encoding a small hairpin ribonucleic acid (“shRNA”) against human mAKAP, and wherein the small hairpin ribonucleic acid comprises the following nucleotide sequence: GGAGGAAATAGCAAGGTTA (SEQ ID NO: 9).
2. A pharmaceutical composition comprising an amount of the composition of claim 1 which is therapeutically effective when administered to a patient in need thereof to protect the patient from heart damage.
3. The composition of claim 1 , wherein the vector is a viral vector.
4. The composition of claim 3 , wherein the viral vector is an adeno-associated virus vector (AAV).
5. The composition of claim 3 , wherein the viral vector comprises human microRNA (miR)-30a sequences.
6. The composition of claim 3 , wherein the viral vector comprises a shRNA minigene, wherein the minigene is flanked by a complete AAV2 inverted terminal repeat (ITR) on the 5′ end and a deleted AAV2 ITR on the 3′ end.
7. The composition of claim 3 , wherein the viral vector comprises a chicken cardiac troponin T promoter.
8. The composition of claim 3 , wherein the viral vector comprises a SV40 polyadenylation site.
9. The composition of claim 4 , wherein the AAV is an AAV serotype 9.
10. A method of inhibiting the expression of human mAKAPβ, comprising contacting mRNA encoding mAKAPβ with the composition of claim 1 .
11. A method of protecting the heart from damage, comprising administering to a patient at risk of such damage, a pharmaceutically effective amount of the composition of claim 1 .
12. A method of treating or preventing heart disease, comprising administering to a patient in need thereof, a pharmaceutically effective amount of the composition of claim 1 .
13. A method of treating or preventing myocardial infarction, comprising administering to a patient at risk of such damage, a pharmaceutically effective amount of the composition of claim 1 .