Gene therapy is a new field in which normal genes are given to patients to cure genetic disorders. Some successes have occurred, as well as some failures. But researchers believe that gene therapy shows promise, because this approach to disease treats the root of the disease instead of just its symptoms.
Three Types of Therapy
Three types of therapy currently exist. In gene replacement therapy, a mutant gene is replaced with a normal gene. In gene augmentation therapy, a normal gene is added but the mutant gene is not removed. And in gene inactivation therapy, a gene is added that will cancel the effects of the defective gene. Sometimes combined to produce the desired cure, the type or types of therapy selected depend on many factors, including whether the actual genetic defect can be pinpointed exactly.
Body Must Be Tricked to Accept Cloned Genes
The point of gene therapy is twofold. First, the gene must be cloned (created), or engineered. This process is also known as recombinant DNA technology (first performed in 1972). Secondly, the normal gene must be introduced into the patient's chromosomes. The body, hoever, actually regards the cloned "normal" gene as foreign, so the it must be tricked into accepting the cure.
Of the various methods tried, the most efficient technique uses an RNA virus called a retrovirus. The retrovirus infects the patient's cells, then copies its DNA into the patient's DNA.
The first human gene therapy was approved for clinical trial in the United States in May 1989. At the end of 1992, at least 37 gene therapy projects were completed, in progress, or approved in China, France, Italy, the Netherlands, and the United States. Each country has its own approval process, designed to protect the patient, the health workers, and the public. By mid-1995 the National Institutes of Health (NIH) and Pharmaceutical Research and Manufacturers of America reported increased efforts in this field. U.S. companies had 57 projects underway, 12 projects completed, and 18 pending, while drug companies had 17 therapies in development.
In the United States, each procedure must be approved by the director of the NIH, by the NIH Recombinant DNA Advisory Committee, and by the U.S. Food and Drug Administration (FDA).
Gene therapy trials have included severe combined immunodeficiency (SCID) and malignant melanoma. SCID is a rare disease that prevents the person's immune system from functioning. This well-publicized study concerned the teenager named David who lived for several years in a plastic bubble to protect him from infection.
Some cases of SCID result from ADA deficiency, a genetic mutation that prevents lymphocytes from producing the enzyme adenosine deaminase (ADA). Lymphocytes are white, or nearly colorless, cells in the blood and lymph systems produced either by the bone marrow (B cells) or by the thymus (T cells). T cell lymphocytes are the major players in the body's immune system, which does not develop normally without the enzyme ADA.
In September 1990 NIH researchers R. Michael Blaese and W. French Anderson performed the world's first gene therapy on a four-year-old child with SCID. A normal gene for ADA was inserted into a virus and allowed to "infect" lymphocytes that had been withdrawn from the child's body. Then the girl was injected with the altered cells. During the next 18 months, the patient had several series of injections, along with other treatment. A second patient, a nine-year-old girl, had similar treatments. The cells encouraged production of ADA in both children, who attended school, had only the normal number of infections, and reportedly experienced no side effects. Since then similar treatments have been used on children in other countries.
Many gene therapy studies have been completed or are underway for various cancers. In a study of the skin cancer melanoma, doctors withdrew a sample of the patient's own cells, inserted an altered gene, and returned the new cells to the patient. The purpose of this procedure is to introduce a protein that will kill the melanoma tumor.
Cystic Fibrosis Study Yields Few Results
A gene therapy study for the lung disease cystic fibrosis began in 1992. The therapy calls for inserting a needed gene into an engineered cold virus (the virus is altered so that it will not cause a cold), which the patients inhale. The gene enters the lung and improves cell function, preventing the production of the mucus (a slimy secretion) that blocks a patient's breathing.
The genes performed precisely under laboratory conditions, but in human studies, less than one percent of patients achieved the desired results. The results are not considered to be sufficient enough to be promising.
Another study concerned familial hypercholesterolemia, a condition in which patients lack a gene for disposing of harmful low-density lipoprotein cholesterol (the so-called "bad" cholesterol). These patients develop a build-up of this low-density cholesterol in their bodies. People lacking both copies of the gene usually die from a heart attack in their early teens. Some-one with only one copy suffers from severe coronary (heart) disease. Scientists at several medical centers are studying insertion of the needed gene into cells from a patient's liver, then injecting the cells into the person's body.
Scientists in China are studying the bleeding disease hemophilia B, which occurs in people whose blood lacks clotting Factor IX. Researchers are attempting to engineer cells with this factor. Studies are also underway on gene therapy for AIDS, liver failure, leukemia, brain tumor, various cancers, rheumatoid arthritis, Gaucher's disease (a metabolic disorder), and various other inherited diseases.