Cardiovascular Diseases

Many gene therapy efforts are focusing on treatment of patients with isolated areas of heart damage, since technology to reach all of the cells in the heart is still being developed. Additionally, in most cases of acquired heart disease, injury is restricted to discrete zones. Cell therapy is also being developed to treat acute cardiac events such as a heart attack and chronic cardiovascular diseases (congestive heart failure, cardiomyopathy, peripheral vascular disease). The status of the developing gene and cell therapy treatments for cardiovascular diseases are described in greater detail here.

Cardiovascular diseases can be divided into congenital diseases (diseases present at birth) and diseases acquired during life. The development of gene therapy for diseases of the heart is challenging in part because of difficulties in delivering gene therapy to a majority of cells in the heart. Preclinical studies (i.e., studies in cultured cells and animals) aimed at developing gene therapy for congenital heart disease are ongoing and include development of methods to overcome these challenges. Pompe disease is a congenital disease that results from a mutation in the gene encoding the essential enzyme alpha glycosidase. People who have this mutation often have muscle weakness, including weakness of the heart muscle and of the muscles that are critical for breathing, such as the diaphragm. These patients may succumb from heart failure or respiratory failure. A gene therapy trial that uses a vector to deliver a normal alpha glycosidase gene to the diaphragm will begin recruiting patients in the near future. An example of gene therapy for an acquired disease is the development of approaches to help the heart heal after a heart attack. One of these approaches involves increasing production, in the heart, of a molecule that stimulates the formation of new blood vessels and thereby helps the heart to heal. Several gene therapy strategies to treat abnormal heart rhythms (“arrhythmias”) are being tested in preclinical studies. Many of the obstacles in developing gene therapy for arrhythmias as well as the strategies for overcoming them have been recently discussed (Donahue, 2007). Arrhythmias can affect the whole heart in some patients; however, other patients have localized arrhythmias, generated in only one part of the heart. A gene therapy approach that is aimed at treatment of these localized arrhythmias is expected to be tested soon in a clinical trial. As vectors and vector delivery methods improve, gene therapy for cardiovascular diseases will likely expand.

Cell therapy is being developed to treat both acute cardiac events such as heart attacks, as well as chronic cardiovascular diseases such as congestive heart failure and peripheral arterial disease. Theoretically, local replacement of cells that were lost due to a heart attack will enhance repair and recovery. Some cell therapy strategies involve the use of “autologous” (i.e., taken from the same patient) “stem” cells. Stem cells are capable of differentiating into all cell types, including heart cells. Transplantation of bone marrow, which includes small numbers of stem cells, is also being investigated as a treatment for heart attacks. Other labs are developing “off the shelf” stem cell products that are not autologous but instead can be used to treat all patients. One of the unique challenges of cell therapy for heart disease involves the ability of the new cells to make sufficient connections with the existing heart cells. These connections are required in order to maintain the electrical currents that are needed for the heart to beat in an organized, efficient manner. Various cell therapies for the treatment of scar tissue from a heart attack are being tested in phase I, II or III clinical trials. So far, cell therapies have been able to increase the heart’s efficiency by a small, but encouraging amount: about 5%.

In addition to offering novel treatments for cardiovascular diseases, gene therapy and cell therapy approaches also provide methods that allow an understanding of important interactions between cells, that identify signals and markers, and that reveal critical healing signals. Insights gained with these approaches can in turn be used to develop new therapies.

For more information on cardiovascular disease, please visit the following websites:

American Heart Association
Cardiovascular Disease Foundation

Please consult your physician before making any medical decisions.