Research Progress toward Gene Therapy
Miller, Julie Ann, Science News
Rapid advances in laboratory research during the last few months have made the rare immune system disorder called adenosine deaminase deficiency likely to be the target of the first U.S. experiments in human gene therapy. In as little as two months a group of researchers from several institutions, led by W. French Anderson of the National Institutes of Health (NIH) in Bethesda, Md., may be ready to propose an experiment in which a normal human gene for adenosine deaminase (ADA) is transferred into bone marrow cells, which will then be returned to a patient. Currently, persons with ADA deficiency die early in childhood unless they receive a bone marrow transplant from a suitable donor.
The most striking laboratory data so far demonstrate the "correction" of defective immune system cells taken from a youngster with ADA deficiency, R. Michael Blaese of NIH reported this week in Gmienden, Austria, at the Workshop on Primary Immunodeficiency Diseases. In the disease, the lack of ADA enzyme allows the buildup of 2' deoxyadenosine triphosphate, a chemical that is particularly detrimental to immune system cells, especially T cells. Blaese and Don Kohn have demonstrated that after the transfer of a normal ADA gene, T and B cells of the ADA patient act like normal immune system cells.
Although excited by the data, Anderson said in an interview, "We're not ready to treat this patient tomorrow. There are still a lot of things that need to be done." The researchers plan to make a formal proposal for a human gene-therapy experiment, he says, after they get results on monkey experiments, expected in the next two months.
Currently about a half dozen U.S. patients are candidates for such a genetransfer experiment. These are children for whom there is no suitable bone marrow donor. This situation contrasts with that for Lesch-Nyhan disease, another enzyme deficiency that had been considered a likely focus of early genetic engineering attempts. Progress there has been slowed by the recent failure of a bone marrow transplant from a normal donor to ameliorate the disease.
Another important advance toward gene therapy was reported by Anderson earlier this month in Los Angeles at a meeting on tissue-specific expression of cloned genes. He and NIH colleagues Philip Kantoff and Martin Eglitis transferred a gene into mouse bone marrow cells. When the cells were transplanted into mice whose own bone marrow had been destroyed, they repopulated the marrow and after four months continue to produce cells containing the foreign gene. Most important, the gene transplanted into the animal's B and T cells produces its characteristic protein. …