Separate Experiments Suggest Gene Therapy Works Two Reports Detail Successes In Patients Treated With Healthy Genes

A full, detailed report on two young Ohio girls who got the world’s first authorized gene therapy treatments suggests the pioneering treatments did work, although doctors cannot yet claim cures.

The results, published Thursday in Science magazine, show that Cindy Cutshall and Ashanti DeSilva both lead normal lives, free from the fear of deadly infections. Before treatment, both girls were kept home, isolated to minimize contact with microbes.

According to the report, the girls’ immune function has continued to improve - even though their use of a special drug, PEG-ADA, has been halved. This is the strongest evidence yet that the inserted genes are working, scientists said.

A second report, also in Science, deals with two young boys in Italy - both about 2 years old when gene treatments began in March 1992 and July 1993. Within six months, both boys showed long-term survival of their engineered white blood cells, and immune function had greatly improved.

“This is what people have been clamoring for: evidence that you can actually improve someone’s health with gene therapy,” said Dr. R. Michael Blaese, chief of the clinical gene therapy branch at the National Institutes of Health. “There is absolutely no question that it works.”

The target of such experiments is a rare inherited disorder called ADA deficiency. Because of a damaging gene mutation, such children are unable to make a normal enzyme, adenosine deaminase, or ADA, to keep their immune cells, T-cells, healthy. As their T-cells die, immunity disappears and the children become dangerously susceptible to infection, even by ordinarily benign microbes.

The gene treatment, by replacing the damaged gene, leads to production of the enzyme, which apparently rescues the patient’s T-cells, re-establishing protective immunity.

What is most in question, however, is whether actual cures have been achieved. In the Ohio girls, new genes were inserted into mature, circulating white blood cells, rather than into their bone marrow cells. So doctors worry that the benefit may go away as the white blood cells die off.

Blaese noted, however, that the benefit has continued, and has even improved in the two years since the injections of genetically altered cells ended. This indicates that the engineered cells have persisted and, most important, that the engineered cells gained a growth advantage, surviving better than damaged cells.

Similarly encouraging results were seen in the Italian experiments.