Methods and compositions for correction of cardiac conduction disturbances

Patent Number: 7,494,644

It is known that bone marrow stem cells are mobilized after heart injury such as infarct, with presumable therapeutic effects mediated by the stem cells in terms of stimulating angiogenesis or even integrating into the damaged myocardium and transdifferentiating into de novo cardiomyocytes. 

One of the problems of stem cell therapy for cardiac conditions is that proper gap junctions are not always formed correctly between the stem cells (endogenous or exogenous) and the existing myocardial cells.  This is particularly relevant when investigators are using skeletal myoblasts, which sometimes do not form appropriate communication channels with the existing cardiac cells and as a result arrythmias occur. 

Connexin-43 is protein that makes gap junctions in the heart and brain.  Interestingly transfection of connexin-43 into glioma cells
induces their differentiation.

The current patent teaches the transfection of cells that will be used for cardiac repair with connexin-43.  This would allow for more efficient integration and communication between the administered cells and the existing cells. 

The claims are broken down into three independent sets. 

The first essentially covering the method for creating an electrical connection between a mammalian cell that is "recombinant" and a myocardial cells.  This is accomplished by altering the recombinant mammalian cell so as to express connexin-43.  The mammalian cell may be a skeletal muscle cell or mesenchymal stem cells, autologous or allogeneic, and also the recombinant cell is administered by injection into the patient's cardiac tissue or by cardiovascular infusion.

The second independent claim is similar to the first except it is restricted to skeletal muscle cells and does not mention mesenchymal stem cells.

The third independent claim covers the "treatment of a cardiac conduction disturbance" in the host through essentially the same means as the other 2 independent claims.

This patent would be useful for almost anyone working in the area of cardiac cellular therapeutics.  Although some are rather cautious of "gene therapy", it should be noted that companies such as Celladon are actually in Phase II with gene therapeutic approaches for heart failure.

View this patent on the USPTO website.