A New Start for Gene therapy?(COMMENTARY)

Article excerpt


Just weeks ago, gene therapy celebrated one of its greatest successes, the almost-miraculous cure of a 2-year-old Dutch child afflicted with "bubble boy syndrome." His severe combined immunodeficiency (SCID) forced him to live hermetically sealed in plastic. But by removing stem cells from his marrow, genetically modifying them, and re-injecting them, researchers gave him a shiny new fully functional immune system.

Now such SCID treatments in the United States have ground to a halt. Why? Similar therapy, which had cured a 3-year-old French boy, has given him a leukemia-like illness.

Gene therapy has always been controversial, mostly because it got off to a promising start and then floundered for almost a decade. But it's now the "comeback kid" of biotech, and is involved in more than 600 clinical trials in 20 different countries.

Gene therapy shows promise not just against SCID but many hereditary disorders. About 5 percent of children worldwide are born with congenital or hereditary problems, and nearly 40 percent of adults are thought to have some genetic predisposition from minor ailments to killers like cancer and sickle cell anemia.

Originally, the purpose of gene therapy was precisely what the "bubble boy" doctors did: Treat a disease caused by a single defective gene by substituting a good one for a bad one. Then scientists made a discovery that changed all that. They found that adding genes that caused the right proteins to be produced could potentially alleviate any number of disorders.

Gene therapy is being applied to problems ranging from Parkinson's to heart disease to AIDS, although about two-thirds of the clinical trials are for cancer. A rodent study at Jefferson Medical College in Philadelphia was spectacularly successful in actually preventing the animals from developing stomach cancer after they were heavily dosed with a powerful carcinogen. Further, the genes were delivered orally. Can anyone say: "Cancer prevention pill"?

Looking further, the researchers found that among 26 different cancer cell lines - including tumors of the lung, head and neck, esophagus, stomach, cervix, pancreas and kidney - the new genes inhibited tumor cell growth in more than half of the experiments.

The tragic case of the French toddler must be seen as a lesson, not the end of the road. And part of that lesson is that using viruses to insert and spread the corrective genes appears to have major limitations.

All of the early gene therapy experiments took advantage of the infectious power of viruses, which by nature burrow into the nucleus of living creatures and set up house.

Viruses comprise a small piece of DNA or RNA stuffed inside a protein envelope. Researchers render the virus theoretically harmless by deleting some or all of its genes. …