Gene Therapy To Lower Blood Pressure Just Enough

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

The gene in question -- atrial natriuretic peptide or ANP -- promisesto control blood pressure through a variety of effects on key areasinvolved in the problem of hypertension, including the relaxation ofsmooth muscle cells in blood vessels, increasing the vessels'diameters, and reducing the manner in which the vessels react to agentsthat can constrict those vessels. ANP also improves the manner in whichthe kidney eliminates sodium or salt from the body and inhibits othersystems, such as the sympathetic nervous system, believed linked todevelopment of high blood pressure.

"This makes ANP an attractive agent for use in treating bloodpressure," said O'Malley. "However, its use is limited by the fact thatit 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 lowlevels, said O'Malley. Obviously, a method of controlling the gene andthe amount of ANP a cell makes was needed.

The special viral vector developed by O'Malley and his colleaguescombines a special kind of adenovirus altered so it does not producedisease connected to a gene regulatory system turned on by the drugmifepristone.

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

One question that remains is whether the body will accept repeatedinjections of the viral vector or whether its immune system eventuallyreact against it, said O'Malley.

Others who participated in thisresearch include Drs. Kurt J. Schillinger, Sophia Y. Tsai, George E.Taffet, Anilkumar K. Reddy, Ali J. Marian, Mark L. Entman, KazuhiroOka, and Lawrence Chan, all of Baylor College of Medicine. Thisresearch was funded by the National Institutes of Health.