Gene therapy on heart disease has one of three goals:
To change or fix an abnormal gene so that it is normal.
To inject healthy genes into the body to compensate for an absent or weakly functioning gene.
To replace an abnormal gene with a normal one.
Research on gene therapy as a treatment for cardiovascular conditions includes:
ADD2 and SLC9A2 have been identified as “blood pressure genes.” Further study may enable the detection of individuals with either of these genes. This, in turn, can help researchers assess the risk for developing high blood pressure and propose the best treatment strategies. Both genes have been associated with increased performance of some heart medications, including beta blockers and diuretics.
Akt1 is a gene shown to prevent death of transplanted cells. Scientists have added this gene to bone marrow cells that, when injected into animal heart muscle damaged by a heart attack, resulted in an 80 to 90 percent increase in the heart’s pumping ability.
Gene therapy for peripheral arterial disease led to the growth of new blood vessels in the legs, which delivered much-needed blood to the oxygen-deprived tissues near the blockages.
An endothelial lipase gene is shown to control HDL (so-called “good”) cholesterol levels. Further studies may be directed to drugs to interfere with the gene’s HDL-lowering effects.
Certain molecules (matrix metalloproteinases) cause the rapid growth of cells after bypass surgery, which can eventually close the newly opened bypass grafts and make another surgery necessary. However, this build-up was prevented with the use of gene therapy, by which the tissue inhibitor of metalloproteinase (TIMP-3) effectively blocked new cell growth in both human and animal laboratory studies.
Gene therapy, using S16EPLN, was found to strengthen the functioning of weakened heart muscle cells in laboratory studies. If this effect is also produced in human beings who have been diagnosed with heart failure, it may help to reverse the condition.
A gene for a protein called S1001A1 was shown to improve heart failure among lab rats when injected. Researchers injected the gene into rats 12 weeks after simulating a heart attack. After about a week, the rats’ hearts began to function normally.
Mutations (changes) in the gene GATA4 have been associated with congenital heart disease, specifically damage to the muscular wall (septum) that divides the heart’s chambers.
Mutations found in the gene PRKAG2, located on chromosome number 7, have been linked to Wolff-Parkinson-White syndrome. This is a condition in which the normal electrical signals in the heart are traveling along an extra, abnormal electrical pathway, which can cause an abnormal heart rhythm (arrhythmia). These genetic abnormalities are also associated with cardiomyopathy that is caused by Wolff-Parkinson-White and other diseases of the heart’s electrical conduction system.
Some ethnic/racial groups may have a higher number of variations within genes that can influence a number of cardiovascular conditions. Among black Americans, for example, changes in two genes – alpha2c and beta 1 – may raise blood pressure, constrict blood vessels and increase the risk for heart failure.
Other research is investigating the roles played by the following genes:
AC6 gene. Strengthens the heartbeat and may be helpful in cases of heart failure.
ACE (angiotensin-converting enzyme) I/D gene. May be associated with increased risk of both heart attack and stroke, and could have implications for which people would be most likely to benefit from taking ACE inhibitors. The ACE gene has also been linked to a higher risk of high blood pressure in men, although no link has been found in women, as well as the type and distribution of body fat among obese people.
Alu gene. Identified as a possible marker for heart attack.
A variant of the Apolipoprotein E (apoE-4) gene. May be associated with increased risk of heart attack, regardless of cholesterol level. Variations in a particular gene may increase the risk of heart attack. Researchers have found variations specific to males and to females.
Endothelial nitric oxide synthase (eNOS) gene. Mutations (abnormal changes) in this gene may be a cause of coronary artery spasm, as well as a contributing factor to the development of blood clots.
P1A2 polymorphism. People with this type of genetic variation may be more likely to benefit from a daily aspirin than people who do not have it.
P21 gene. Linked with diseases commonly associated with aging, such as Alzheimer's and atherosclerosis (hardening of the arteries).
Specific growth factors are being investigated for their therapeutic angiogenic effects, or the ability to stimulate the growth of new blood cells. Two are basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). There is also a genetically engineered version of bFGF called FGF-2. Growth factors have shown good results in animal studies and are now being tested in clinical trials with human volunteers. For example, infusions of FGF-2 have improved the weakness and pain associated with claudication. In stimulating the formation and growth of new blood vessels, VEGF may reduce certain types of chest pain(angina). VEGF may also enhance balloon angioplasty by reopening many narrowed blood vessels, as well as preventing re-narrowing (restenosis) after the procedure.
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