The problem with gene therapy isn't inserting a gene into a cell - that biotechnology can do - it's getting the gene inserted into enough cells to provide a therapeutic benefit.

Ariad Pharmaceuticals Inc.'s ARGENT (Ariad Regulated Gene Therapy) stem cell therapy technology might help science clear this hurdle. Researchers from Cambridge, Mass.-based Ariad and the University of Washington demonstrated that a small number of genetically modified bone marrow cells could be activated to grow in vivo into a large population. The study was published in the Sept. 15, 2002, issue of Blood. Although the research is in its early stages, Ariad said the technology could hold promise in a range of diseases from thalassemia to diabetes.

"The study was aimed at testing a specific new tool for use in cell therapy," said Timothy Clackson, senior vice president, science and technology at Ariad. "What the study demonstrates is the successful application of this technology in a large animal model."

The large animals, in this case a 9-month-old female beagle and a 24-month-old male, were administered CD34+ cells that had been withdrawn from their marrow and genetically engineered to express a conditional derivative of the thrombopoietin receptor. AP20187, Ariad's ARGENT cell-switch drug, was then given intravenously. Researchers found reversible, drug-dependent increases in genetically modified red blood cells, white cells and platelets in both animals. When AP20187 administration was stopped, "the number of cells dissipated back to near their background levels," Clackson said.

Clarkson and the authors said stem cell therapy has demonstrated unequivocal efficacy in two separately published trials, each for the treatment of X-linked severe combined immunodeficiencies. That success was due to "the tremendous selective advantage conferred upon corrected lymphocytes relative to their unmodified counterparts." But when considering most diseases, the genetically modified cell has no selective advantage, doesn't grow into a large population, and therefore offers no patient benefit. The ARGENT cell-switch drug might be the boost genetically modified cells need to grow to levels that would benefit patients or cure disease.

"This study lays a preclinical groundwork establishing the functionality of this system on the scale near what is required for humans," Clackson told BioWorld Today, adding that further preclinical studies are planned.

Ariad's ARGENT technology is designed to control cellular events through the use of small molecules. While the product featured in Blood has yet to reach humans, Ariad does have a product in the clinic that is based on the ARGENT technology - AP1903 - which is in Phase II trials in graft-vs.-host disease. So while AP20187 is still in animals, Clackson said the cell growth switch also works with the AP1903 drug and has been through Phase I testing.

"We are already one rung up the ladder," he said. "AP20187 is essentially identical to 1903." Ariad plans to present data from the trial at academic meetings as they become available.

Ariad also has AP22594, another ARGENT-based product, in development for anemia and is expecting to file an investigational new drug application next year. For now, the cell growth switch research continues, and Clackson sees the far-reaching possibilities.

"Because this is a general technique, you could use this potentially for any cell type or any gene," he said, giving sickle-cell anemia as an example. "Sickle cell is highly prevalent, highly debilitating and often fatal. If you could install the correct gene into the correct cells and grow them to high enough numbers in vivo, you could cure this disease."

Ariad's stock (NASDAQ:ARIA) rose 34 cents Monday, or 10.4 percent, to close at $3.62.