The premise of gene therapy is straightforward. If something is wrong with your genes -- or you're missing an essential one altogether, for example, resulting in cystic fibrosis or hemophilia -- then gene therapy would simply reintroduce the appropriate, healthy gene into the cells to be incorporated into your existing DNA. The healthy gene would be replicated as new cells formed, and the replacement of defective genes with healthy ones would ultimately cure the disease. At least, that's the theory.
In reality, finessing gene therapy has turned out to be highly complex. Each of the trillions of cells in the human body houses a copy of DNA wrapped tightly in the famous double helix shape.
DNA makes up the 23 chromosome pairs that contain our genes -- 20,000 to 25,000 of them, all told, according to the Human Genome Project, which in 2003 completed the massive task of mapping those genes (and the 3 billion base pairs they contain). Each gene regulates some aspect of the body's development or functioning through its control over a specific protein.
So far, the actual impact of gene therapy has been modest. Research on its use in treating heart disease is mostly in the preclinical stage, meaning that it involves animals or test tubes rather than people.
Studies have shown that gene therapy can stop or even reverse heart failure -- in mice. But trials with human subjects have barely started. Several that are currently recruiting participants, or just recently underway, seek to investigate the use of gene therapy to improve human heart function.
One trial that began in 2008 will assess gene therapy's ability to encourage the growth of new blood vessels in 12 people with heart failure. Another small trial will study the effectiveness of the gene therapy drug, Mydicar (AAV1/SERCA2a), for restoring cardiac function in people with heart failure.
One of the most complex problems scientists have faced involves gene transfer -- that is, how to get healthy genes into the parts of the body where they'll do the most good, without doing harm.
A number of trials have used a specific virus (an adenovirus) as the delivery vehicle. Although the virus is very efficient at replicating DNA in the cells, it may trigger a severe immune response and has been implicated in several deaths. Such setbacks have brought about renewed interest in safer methods for gene transfer.
Since gene therapy remains highly experimental, trials in humans are typically restricted to people with a terminal illness or some other serious condition -- for example, heart failure that's been proven resistant to treatment by all other means.
While the benefits of gene therapy may not materialize for years, stay tuned. If its promise is realized, it could herald truly significant medical advances.
Sources:
"Cellular Therapy: Potential Treatment for Heart Disease." fda.gov. 21 Jun. 2004. U.S. Food and Drug Administration. 16 Sep. 2008 <http://www.fda.gov/Cber/genetherapy/celltherapyheart.htm>.
"Genes and Gene Therapy." MedlinePlus. 31 Jul. 2008. U.S. National Library of Medicine and the National Institutes of Health. 16 Sep. 2008 <http://www.nlm.nih.gov/medlineplus/genesandgenetherapy.html#cat27>.
"Genetics Home Reference: Your Guide to Understanding Genetic Conditions." ghr.nlm.nih.gov. 3 Oct. 2008. U.S. National Library of Medicine and the National Institutes of Health. 13 Oct. 2008 <http://ghr.nlm.nih.gov>.
Periasamy, Muthu, Anuradha Kalyanasundaram. "SERCA2a Gene Therapy for Heart Failure: Ready for Primetime?" Molecular Therapy. 16:6(2008): 1002-04. <http://www.nature.com/mt/journal/v16/n6/abs/mt200889a.html> (subscription).
