Gene therapy to lower blood pressure just enough

September 27, 2005

HOUSTON -- (Sept. 27, 2005) --- A newly developed virus that introduces a blood pressure-lowering gene into cells and enables that gene to maintain blood pressure at healthy levels for four months promises to take gene therapy for the disorder a step closer to reality, said researchers at Baylor College of Medicine in a report released online in the Proceedings of the National Academy of Sciences.

"High blood pressure is one of the leading causes of death and disability in adults worldwide," said Dr. Bert O'Malley, chair of the BCM department of molecular and cellular biology. "A therapy that could control blood pressure could have important benefits for individuals and for the health of the world's population as well."

The gene in question -- atrial natriuretic peptide or ANP -- promises to control blood pressure through a variety of effects on key areas involved in the problem of hypertension, including the relaxation of smooth muscle cells in blood vessels, increasing the vessels' diameters, and reducing the manner in which the vessels react to agents that can constrict those vessels. ANP also improves the manner in which the kidney eliminates sodium or salt from the body and inhibits other systems, such as the sympathetic nervous system, believed linked to development of high blood pressure.

"This makes ANP an attractive agent for use in treating blood pressure," said O'Malley. "However, its use is limited by the fact that it has such short-lived activity in the blood system."

Its activity is halved 30 seconds after it enters the blood stream.

Gene therapy can make cells generate more ANP. In previous studies, however, this kind of gene reduced blood pressure to dangerously low levels, said O'Malley. Obviously, a method of controlling the gene and the amount of ANP a cell makes was needed.

The special viral vector developed by O'Malley and his colleagues combines a special kind of adenovirus altered so it does not produce disease connected to a gene regulatory system turned on by the drug mifepristone.

Using this vector, O'Malley and his colleagues were able to introduce the ANP gene into the cells of mice. Then tiny doses of drug turned on the regulatory system, which controlled the amount of ANP made so that blood pressure remained at healthy levels for 125 days - 74 days longer than in any previous gene therapy study. Other studies indicate that the therapy could reduce the heart-weight/body-weight ratio. For this reason it has promise in reducing some of the organ damage that occurs as a result of high blood pressure.

One question that remains is whether the body will accept repeated injections of the viral vector or whether its immune system eventually react against it, said O'Malley.
-end-
Others who participated in this research include Drs. Kurt J. Schillinger, Sophia Y. Tsai, George E. Taffet, Anilkumar K. Reddy, Ali J. Marian, Mark L. Entman, Kazuhiro Oka, and Lawrence Chan, all of Baylor College of Medicine. This research was funded by the National Institutes of Health.

Baylor College of Medicine

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