Feature: Discovery at a Cost - Gene Therapy

New scientific discoveries have always come at a cost. In the past, explorers who ventured from Europe to discover the new world did not always come home. Exploration of space has also come at a cost with the January 28, 1986 Challenger space shuttle disaster as an example. Even in medicine, new scientific discoveries come at a cost. Just recently, a three year old French boy undergoing gene therapy for a fatal immunodeficiency disease called SCID exhibited signs of cancer like illness². In 1999, a teenaged boy died after receiving gene therapy in a research study at the University of Pennsylvania's Institute of Human Gene therapy. Yet, 17 other individuals in the same study did not suffer the same level of inflammatory response³. Clearly not all is understood. We only now begin to sail the sea of gene therapy discovery. With this in mind, what is gene therapy? What stage of progress are we, and what does gene therapy offer in the future?

Thousands of genes are arranged on the length of the deoxyribonucleic acid (DNA). This DNA contains all the information that is needed to make the body's proteins. Proteins are found in every living cell and are involved in every function and structure of the cell. DNA is the blueprint of life. Every cell in the body contains its DNA in a compartment called the nucleus (see Figure 1⁴). At times the DNA is damaged which results in disease.

In gene therapy, the damaged DNA is replaced by normal DNA⁴. This approach to medicine may help fight diabetes, cancer, heart disease, and high blood pressure. It may also give new treatment regimes to patients with incurable diseases such as cystic fibrosis, hemophilia, and severe combined immunodeficiency disorder (SCID) like the little French boy⁵. This approach sounds simple, but is very difficult to achieve.

First, normal DNA must be packaged for delivery in such a way that the cell's methods of protection from foreign matter invasion are overcome. A packaging system, known as a vector, would ideally be easy to produce while being non toxic to the cell, not be attacked by the immune system, and efficient at delivering the DNA to a specific cell. To date, no such transport system (vector) that meets all these criteria exists¹.

Current packing systems (vectors) being used are: naked DNA, modified viruses, synthetic chemical vectors, fat hollow spheres called Liposomes, and protein DNA complexes¹.

Once normal DNA is transported by a vector to the nucleus of the cell in the damaged tissue, the DNA is unloaded (see figure 2⁴). Then, the normal DNA can start to produce the missing or damaged proteins, thus allowing the cell to repair itself⁴.

In the case of the French child who presently has cancer like symptoms, another 9 children have been cured by the same gene therapy. The French trial run by Dr. Alan Fischer takes the normal gene, which is a segment of DNA, and inserts the gene into bone marrow cells using a vector. The bone marrow cells are then transferred to the patient in need of normal bone marrow cells. The new bone marrow cells create the immune system the patient is lacking^{2 4}. The problem with the one child is thought to be that the gene was inserted into a portion of the DNA that can potentially cause leukaemia².

Research to produce abundant quantity of vectors that can transfer various size DNA segments with fewer side effects is required and ongoing. In addition, research to ensure that DNA is delivered to the correct location is currently underway¹.

Gene therapy has the potential to possibly eliminate the cause of disease such as SCID and cystic fibrosis. Gene therapy also has the potential to aid in the treatment of diseases such as cancer, diabetes, heart disease, AIDS, and rheumatoid arthritis¹.

Lessons are being learned from research failures and as a result, tighter regulatory controls have been called for on future research. Gene therapy is a long ways away from use in the medical community as a normal practice, but when it does arrive, it will change the way medicine is conducted.

References: Discovery at a Cost - Gene Therapy

1. Balicki, D and Beutler, E. 2002. Reviews in Molecular Medicine. Gene Therapy of Human Disease. Medicine 81(1)
2. Check. E. 2002. Regulators split on gene therapy as patient shows signs of cancer. Nature 419:545
3. Dean, D. A., and Perkin, R. A. 2001. Medicine and Society. Gene therapy: If at first you don't succeed… American Family Physician. 63:9
4. FDA1. 2000. Fundamentals of Gene therapy. www.fda.gov/features/2000/gene.html
5. FDA2. 2000. Human Gene therapy and the role of the food and drug administration. www.fda.gov/cber/infosheets/genezn.htm

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