Nov. 12, 1999 (Atlanta) — Researchers have
used gene therapy to essentially cure high blood pressure, also called
hypertension, in rats and their offspring, according to a study published in
the Nov. 12 issue of Research Circulation: Journal of the American Heart
Association.
The researchers used an inactive virus to
introduce the new gene into newborn rats (specially bred to develop high blood
pressure) and found that it prevented the development of hypertension for life.
“And when you breed these rats … the antihypertensive effect is
transmitted to at least two generations of offspring,” senior author Mohan
Raizada, PhD, tells WebMD. “The reason we feel it’s important is, this is
the first time a therapeutic gene is being introduced and its effect, or its
consequence, is expressed in the offspring.” Raizada is a professor of
physiology at the University of Florida College of Medicine in
Gainesville.
The researchers decided to try to attack a
system in the body that is vital in the control of blood pressure, known as the
renin-angiotensin system. Blocking this system with medications leads to a
significant improvement in hypertension. Medications that act on this system
are called ACE inhibitors and include such drugs as Vasotec (enalapril
maleate), Prinivil (lisinopril), and Altace (ramipril), and many others. In
addition, a newer class of medications called angiotensin receptor blockers,
including Cozaar (losartan potassium) and Diovan (valsartan), also block this
system but in a slightly different way.
“So we thought if we are going to try
to test gene therapy, we should use the same approach [as the drugs]. So what
we did is we tried to inhibit the expression of the renin-angiotensin system
… at the genetic level,” says Raizada.
“When we found [no hypertension] even
when the [rats] were 200 days old, which is almost like old age for the rats,
we decided to extend the experiment and see if it [was present] in the
offspring. This is really kind of an offshoot of the [original] study,”
says Raizada.
To test their hypothesis, the researchers,
led by Phyllis Reaves, PhD, divided regular rats and the specially bred rats
into two groups: half of each group received a shot of gene therapy; the other
half received a shot of an inactive chemical. At 100 days, two sets of parents
from each of the four groups were bred to generate offspring; the offspring
were similarly bred to generate the next generation of offspring. The animals
all had their blood pressure monitored at various times during the study. In
both generations, offspring of the gene therapy rats had significantly lower
blood pressure compared with the offspring from the other rats. Raizada says
he’s not sure why or how the effect of this particular gene therapy appears to
be passed on to future generations.