made it possible to collect enough stem cells so that these cells migrate back to the patients' bone marrow, where they regenerate the full repertoire of blood cells. The gene-therapy experiment proposed by the NIH group will be similar to the bone transplants, but they will rely on An NIH advisory committee gives the nod to a new strategy marrow CD34-positive cells taken from the bloodstream. And in the NIH study the CD34for genetic therapy based on a rare type of blood cell positive cells will be treated with the normal ADA gene before they are given back to the IF A PROPOSED EXPERIMENT AT THE NA- for delivering the normal ADA gene, both children in a transfusion. The hope is that tional Institutes of Health gets the expected because they are immortal and because they enough stem cells will carry the normal gene go-ahead, gene therapy may move one step give rise to all the body's blood cells. Thus, if and accumulate in the patients' bone marrow closer to the long-awaited goal of curing- the defect could be corrected in these cells, all to produce healthy blood cells that restore not just treating-inherited diseases. the subsequent white cells that originate from immune function. The method isn't without snags, however. Originally, researchers feared that the them should be healthy. toughest problem in gene therapy would be But when Anderson, Blaese, and their col- To collect enough white blood cells for a coaxing the inserted gene to perform prop- leagues began their SCID gene-therapy trials transplant, patients have to endure from three erly, but that hasn't turned out to be the in September 1990, there was no simple way case. Instead, the main roadblock has been to target these cells because they are so rare. getting the gene into the best target cells, Even in the bone marrow, stem cells account _z I~~~~~~~~~ especially the stem cells ofthe bone marrow, for only one in every 10,000 to 100,000 cells, which until now have defied all efforts to and they are even rarer in the blood, averagisolate and manipulate them. ing about one in a million. Instead, the NIH But now a team of NIH researchers, led by team has been inserting the ADA gene into W. French Anderson of the National Heart, mature white blood cells, which-unlike stem Lung and Blood Institute, and R. Michael cells-have a short lifespan. The treatments Blaese and Kenneth Culver of the National seem to be shoring up the immune system as Cancer Institute, thinks it has found a way to hoped, the researchers say. But, this approach insert genes directly into stem cells. It relies cannot cure the disease because the corrected on an innovative commercial technique for cells eventually die and must be replenished. identifying and concentrating the few stem Since the NIH gene-therapy experiment to 10 repetitions of a 6-hour procedure cells that circulate in the bloodstream-a began, however, several research teams and known as leukophoresis, says Curt I. Civin., technique that's now undergoing improve- biotech companies have been working on a director of pediatric oncology at Johns ment in a number of labs, including one technique for ferreting out stem cells, using a Hopkins University. The CD34 cells are then whose work is described in this issue of Sci- monoclonal antibody that recognizes a cell purified from the pooled white blood cells. This process should become less arduous ence (see page 1137). The NIH team wants surface marker called CD34. The cornerto try it as part of its ongoing gene-therapy stone ofthe new Anderson-Blaese protocol is for patients as researchers improve techniques experiment, the first such venture approved, a CD34-based stem cell collection system for increasing the quantity of stem cells in the to treat two young girls with now being marketed by blood. Current methods rely on treating the severe combined immune deCellPro Inc., a biotech firm in patient with the white blood cell growth Bothell, Wash. CD34 does factor called granulocyte colony stimulating ficiency (SCID). Says Anderson: "We're talking about the not recognize stem cells ex- factor (G-CSF). A mixture of additional possibility of a cure." clusively, since between 1% growth factors should yield even greater That strategy took a big and 3% of all bone marrow quantities. "Once we get the right cocktails, cells carry the CD34 marker, one leukophoresis will be enough," predicts step toward realization on 11 February, when the NIH Reincluding an unknown frac- Hopkins' Civin. The scientific "bartending" combinant DNA Advisory tion of stem cells. But the needed to formulate these cocktails is proCommittee gave the team NIH investigators think that gressing rapidly. Tsvee Lapidot and colit could be specific enough leagues at the Hospital for Sick Children in permission to add this new for gene therapy, based on Toronto, for instance, working with SCID technique to its existing protocol. Although the experiprevious experiences using mice receiving human bone marrow, have ment must still be approved this system in bone marrow used a unique growth factor combination W. FrenchAnderson that generates all the red and white cells by NIH director Bernadine transplantation. Healy and by the Food and Over the past 3 years, re- normally found in human blood; their work Drug Administration, no snags are expected. search teams from CellPro and the Fred is decribed in this issue of Science. But AnderSCID is an inherited illness that destroys Hutchinson Cancer Research Center have son', Blaesel, and Culver aren't waiting for the body's immunity against even normally shown that collecting CD34-positive cells additional refinements. If the approvals come innocuous infections. Because of a defective from the bone marrow, pooling them, and as expected, their new experiment could gene, SCID patients are missing an enzyme, using them without any other cells can re- start this summer. a LARRY THOMPSON adenosine deaminase (ADA), that protects place the bone marrow, says Ronald Berrencertain white blood cells from a metabolic son, vice president of biological research and Larry Thompson is a free-lance writer based toxin. The stem cells would be an ideal target medical affairs at CellPro. The technique has in Washington, D.C.

Gene Therapy Moves Toward Approval Stem-Cell

Downloaded from on March 27, 2016

A4~~~~~~~~~~A

1 072

SCIENCE, VOL. 255

Stem-cell gene therapy moves toward approval.

made it possible to collect enough stem cells so that these cells migrate back to the patients' bone marrow, where they regenerate the full repertoire...
354KB Sizes 0 Downloads 0 Views