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Gene therapy for brain tumors
  
By Bijal P. Trivedi

Cellular "Trojan horses" that travel through the brain and destroy invasive tumor cells are currently being tested in mice. The work was reported in a recent issue of Molecular Therapy.

The researchers are using neural stem cells, which would normally grow and differentiate into a range of brain cells, to migrate through the brain and deliver a virus that infects and destroys replicating tumor cells.

Brain tumors are almost untreatable because the tumor cells move around evading removal by surgery or by targeted destruction using chemotherapy, radiation or gene therapy, says Evan Snyder, of Children's Hospital in Boston. "Stem cells are the perfect vehicle to seek and destroy tumor cells, because they are inherently migratory cells," Snyder adds.

The virus carried by the neural stem cells is a mutant version of the Herpes simplex virus type one (HSV-1). The mutation prevents the virus from replicating in all but dividing cells. To prevent the virus from killing the carrier cells, the researchers pretreated the neural stem cells with mimosine, a chemical that halts development and replication, allowing HSV-1 to be carried safely.

The stem cells, which are growth-arrested and virus-bearing, are then injected into gliomas that have been transplanted into mice. As the stem cells migrate through the tumor and beyond, the mimosine gradually diffuses out of the cell until the level drops so low that the carrier cells begin to grow again and replicate. When the stem cells replicate, the chemical changes trigger virus replication that quickly kills the carrier. The virus then infects surrounding tumor cells.

The report shows that these cells are able to carry the virus, and migrate from one side of the mouse brain to the other, says Snyder. More work is needed to determine the therapeutic merits of this method. Using stem cells to attack tumors in other organs has not been investigated, according to Snyder. Before human trials can be contemplated, Snyder and his colleagues will also need to determine whether the virus poses a threat to other stem cells in the body.

"I feel pretty good that this method could be the glue that holds together other therapies," says Snyder. Ultimately stem cells could be a general method used to deliver a specific gene, or any anticancer drug. "This will open up a whole new avenue of gene therapy."

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Herrlinger, U. et al. Neural precursor cells for delivery of replication-conditional HSV-1 vectors to intracerebral gliomas. Mol Therapy 1, 347-357 (April 2000).
 

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