After years of promise and preparation, the first attempt to treat a hereditary disease by installing new genes in a patient's cells is about to begin at the National Institutes of Health (NIH). Scientists there plan to file a proposal today to transfer copies of the correct version of a human gene into the white blood cells of children who, because they inherited a defective version, suffer severe combined immunodeficiency _ a rare disease that destroys the immune system.
In the past, these children, such as the famous Texas "bubble boy," sometimes lived their shortened lives in sterile plastic enclosures that protected them from all bacteria and viruses. Today, the children either receive bone marrow transplants if a donor can be found or are treated with weekly injections that replace the missing enzyme that the defective gene was supposed to make. For lack of the enzyme, the immune systems fail to work. Neither treatment is perfect; the NIH researchers hope ultimately to cure the children by permanently replacing the defective gene.
Although fewer than two dozen people are known to have the disease in the United States, the NIH plan is significant because gene therapy, as the method is called, is considered a promising way to treat many more common genetic diseases.
"This is the first time that a proposal for gene therapy .
. has been formally submitted," said LeRoy Walters, an ethicist from Georgetown University and chairman of a key federal committee that must approve the proposed experiment.
In the experiment, the scientists will use a genetically modified mouse virus to carry the human gene for making adenosine deaminase, or ADA, the missing enzyme. The lack of ADA causes the buildup of a toxic chemical that destroys the child's immune system. Replacing the missing enzyme removes the toxin and restores the immune system.
To get the gene into the body, physicians will remove blood from an afflicted child, separate out a certain kind of white blood cell, called a T cell, and cause it to proliferate in the laboratory.
The mouse virus carrying the ADA gene is mixed with the T cells in the laboratory. The virus, which is altered so it cannot cause illness, infects the white blood cells and permanently inserts the human gene it carries. The blood cells start making ADA.
Using a special growth hormone, billions of the genetically modified T cells can be grown in the laboratory and then injected back into the children as a simple blood transfusion.
The scientists, according to an NIH source who asked not to be identified, expect the genetically repaired T cells to function normally and to completely restore the child's immune defenses.
Although the T cells will be permanently altered by the gene therapy, this treatment probably will not provide a permanent cure. T cells only live from weeks to months, so to maintain the effect, the children will have to receive transfusions with genetically engineered cells every few weeks or months.
The current experiment is expected to be proposed by the teams of R. Michael Blaese of the National Cancer Institute and W. French Anderson of the National Heart Lung and Blood Institute. Neither Blaese nor Anderson would discuss the proposed experiments publicly. They said they would wait until the final version of the proposal is actually submitted to federal review committees.
Three NIH committees must review the Blaese-Anderson experiment over the next month, and the first children probably won't be treated before the summer. The experiment also must be approved by the Food and Drug Administration.