Gene therapy – PBS

A treatment for Cystic Fibrosis. A cure for AIDS. The end of cancer. That's what the newspapers promised us in the early 1990's. Gene therapy was the answer to what ailed us. Scientists had at last learned how to insert healthy genes into unhealthy people. And those healthy genes would either replace the bad genes causing diseases like CF, sickle-cell anemia and hemophilia or stimulate the body's own immune system to rid itself of HIV and some forms of cancer. A decade later, none of these treatments have come to fruition and research into gene therapy has become politically unpopular, making clinical trials hard to approve and research dollars hard to come by. But some researchers who are taking a different approach to gene therapy could be on the road to more success than ever before. - - - - - - - - - - - -

Early Promise

Almost as soon as Watson and Crick unwound the double helix in the 1950's, researchers began considering the possibility- and ethics- of gene therapy. The goals were lofty- to fix inherited genetic diseases such as Cystic Fibrosis and hemophilia forever.

Gene therapists planned to isolate the relevant gene in question, prepare good copies of that gene, then deliver them to patients' cells. The hope was that the treated cells would give rise to new generations of healthy cells for the rest of the patient's life. The concept was elegant, but would require decades of research to locate the genes that cause illnesses.

By 1990, it was working in the lab. By inserting healthy genes into cells from CF patients, scientists were able to transmogrify the sick cells as if by magic into healthy cells.

That same year, four-year-old Ashanti DeSilva became the first person in history to receive gene therapy. Dr. W. French Anderson of the National Heart, Lung and Blood Institute and Dr. Michael Blaese and Dr. Kenneth Culver, both of the National Cancer Institute, performed the historic and controversial experiment.

DeSilva suffered from a rare immune disorder known as ADA deficiency that made her vulnerable to even the mildest infections. A single genetic defect- like a typo in a novel- left DeSilva unable to produce an important enzyme. Without that enzyme, DeSilva was likely to die a premature death.

Anderson, Blaese and Culver drew the girl's blood and treated her defective white blood cells with the gene she lacked. The altered cells were then injected back into the girl, where- the scientists hoped- they would produce the enzyme she needed as well as produce future generations of normal cells.

Though the treatment proved safe, its efficacy is still in question. The treated cells did produce the enzyme, but failed to give rise to healthy new cells. DeSilva, who is today relatively healthy, still receives periodic gene therapy to maintain the necessary levels of the enzyme in her blood. She also takes doses of the enzyme itself, in the form of a drug called PEG-ADA, which makes it difficult to tell how well the gene therapy would have worked alone.

"It was a very logical approach," says Dr. Jeffrey Isner, Chief of Vascular Medicine and Cardiovascular Research at St. Elizabeth's Medical Center in Boston as well as Professor of Medicine at Tufts University School of Medicine. "But in most cases the strategy failed, because the vectors we have today are not ready for prime time." - - - - - - - - - - - - 4 pages: | 1 | 2 | 3 | 4 |

Photo: Dr. W. French Anderson

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Gene therapy - PBS