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    ARTICLE PAGE

    New gene therapy halts 2 boys' rare brain disease

    By AP
    Nov 5, 2009

      WASHINGTON (AP) — French scientists mixed gene therapy and bone marrow transplants in two boys to seemingly halt a brain disease that can kill by adolescence.

      The surprise ingredient: They disabled the HIV virus so it couldn't cause AIDS, and then used it to carry in the healthy new gene.

      The experiment marks the first time researchers have tried that long-contemplated step in people — and the first effective gene therapy against a severe brain disease, said lead researcher Dr. Patrick Aubourg of the University Paris-Descartes.

      Although it's a small, first-step study, it has "exciting implications" for other blood and immune disorders that had been feared beyond gene therapy's reach, said Dr. Kenneth Cornetta, president of the American Society of Gene and Cell Therapy.

      "This study shows the power of combining gene therapy and cell therapy," added Cornetta, whose own lab at Indiana University has long researched how to safely develop gene delivery using lentiviruses, HIV's family.

      The research was published in Friday's edition of the journal Science.

      In 20 years of gene therapy research, there have been few home runs and some headline-making setbacks — including a risk of leukemia caused by otherwise successful gene therapy for another rare disorder, "bubble boy disease." That's a risk that specialists hope a lentivirus-based gene therapy will eliminate.

      Best known from the movie "Lorenzo's Oil", adrenoleukodystrophy, or ALD, is a rare genetic disease that, in its most devastating form, destroys the coating of nerve fibers in boys' brains. Without that coating, called myelin, the neurological system breaks down. The disease typically strikes between the ages of four and 10, leading to blindness, deafness, dementia and loss of muscle control, and killing them within a few years.

      Bone marrow transplants can halt ALD by letting new myelin-forming stem cells take root. But it's difficult to find a matching marrow donor, and the transplant itself is very risky.

      So what if stem cells from the boys' own bone marrow could be genetically corrected, eliminating the ALD mutation? To do that, Aubourg's team had to overcome a technical hurdle: Gene therapy works when scientists harness deliver a healthy new gene by attaching to a virus that can harmlessly infect cells. But none of today's so-called gene therapy "vectors" could penetrate enough of the stem cells needed for an ALD treatment to work.

      Unlike most viruses, HIV can penetrate stem cells, and it sticks permanently. So Aubourg's team removed the genetic parts of HIV that make it dangerous, leaving basically a scaffolding to carry the new therapeutic gene.

      Then they culled stem cells from two 7-year-old boys in the early stages of ALD, and mixed in the healthy gene. The boys underwent bone marrow-destroying chemotherapy and then had their genetically corrected stem cells reinserted.

      Two years later, the boys have shown no sign of worsening brain damage and are functioning well with 15 percent of their blood cells producing the healthy protein, said Aubourg, who plans to test the experimental procedure in more patients. An advocacy group, the Stop ALD Foundation, is working to raise money for a similar U.S. study.

      ___

      On the Net:

      Science Web site: http://www.sciencemag.org

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