Is Gene Therapy for Hypertension Possible?

Because hypertension is a chronic disease of multifactorial and multigenetic origin, it has not been considered appropriate for gene therapy. Gene therapy has tended to be limited to diseases resulting from a single gene mutation that can be replaced by gene insertion or to life-threatening diseases for which there are few alternative treatments, such as glioma and other cancers and rampant HIV infection. Hypertension, in contrast, is controllable by current drug therapies, and although it is a significant risk factor for stroke and heart attack, it lacks the sense of urgency associated with other diseases. The multifactorial nature of hypertension presents a Gordian knot of too many tangles to untie. Gene studies to sort out linkages and associations with hypertension are progressing, but slowly. There have been positive correlations to the angiotensinogen gene1 and recently to the human G protein B3 subunit gene.2 Lifton3 has intensively studied some rare forms of single gene mutations that result in hypertension. However, the causes of essential hypertension remain enigmatic.Nevertheless, drug companies have for years made advances in the control of hypertension with single pharmaceutical targets. The most successful drugs developed to reduce hypertension have been designed to inhibit β-receptors, angiotensin-converting enzyme (ACE) receptors, and recently angiotensin type 1 receptors (AT1-R). Thus, without a genetic linkage study and without a solution to the multifactorial nature of hypertension, drug studies have shown that inhibiting proteins that are overabundant or overactive in plasma or tissue reduces hypertension. The mechanisms of these drug actions are not thoroughly understood. Despite years of β-blocker use for the treatment of hypertension, there has been no generally agreed on mechanism to explain the antihypertensive effects of this class of drugs, yet the Joint National Committee on the treatment of hypertension has regularly recommended their use …