Heart failure is a leading cause of death and disability but neither the cause of hypertension (an underlying factor) or the mechanisms of heart failure are fully understood. It is clear, however, that increased neurohormonal activity accompanies heart failure and ameliorating this activity by beta-adrenergic antagonists and inhibitors of the renin-angiotensin-aldosterone system improves the clinical state. These treatments represent cornerstones in the management of heart failure today.
Much of the pathophysiology associated with heart failure (adverse remodeling of the myocardium associated with a modification of gene expression, an increase in left ventricular mass, depression of intrinsic myocardial function) may be due to abnormal gene transcription that results from aberrant silencing of adult cardiac gene expression and recapitulation of the fetal gene program.
With the above knowledge, researchers at the Department of Veterans Affairs have conducted research towards selectively targeting cardiac gene transcription to alter gene expression, and thereby restore the adult cardiac profile, reduce ventricular mass, and increase contractile function. Their animal model data supports a new treatment for heart failure which accompanies the use of an angiotensin-converting enzyme (ACE) inhibitor, such as captopril (a standard treatment for the management of heart failure) with phenylbutyrate. Phenylbutyrate is a natural nontoxic colorless tasteless aromatic fatty acid purified from mammalian urine and plasma and is Food and Drug Administration approved for children with hyperammonemia associated with inborn errors of urea synthesis
This new approach shows promise for the treatment of heart failure by reversing changes in cardiac gene expression associated with heart failure, biventricular hypertrophy, and myocardial dysfunction.
- The addition of phenylbutyrate to ACE inhibitor results in reversal of changes in transcripts, hypertrophy and myocardial dysfunction associated with heart failure
- Companies can develop the research into a treatment by licensing US patent 9,226,965 and three international patents from the VA
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