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Genetically modified cells migrate to brain and treat neurodegeneration in St. Jude model

Physicians might one day be able to treat a disease that destroys brain cells in children using genetically modified cells to transport a "drug" to the site of the dying neural cells (cells that transmit impulses). This discovery occurred based on results of a laboratory study of the technique published by investigators at St. Jude Children's Research Hospital. A report on this work appears in the prepublication online issue of Blood.

There is currently no cure for such disorders, which are called lysosomal storage diseases (LSDs).

The St. Jude researchers successfully treated a laboratory model of an LSD called GM1 gangliosidosis using bone marrow cells (BMCs) into which scientists inserted the gene for an enzyme that breaks down a fat molecule called GM1. GM1 is a critical component of normal brain cells. But in GM1 gangliosidosis, brain cells lack this enzyme--beta-galactosidase--and GM1 accumulates to such a high concentration that it disrupts the proper function of the cell and causes it to self-destruct. BMCs include a population of so-called pluripotent stem cells--cells that give rise to a variety of different cell types that have specific functions, such as the immune cells called monocytes.

After the St. Jude team infused the genetically modified BMCs into the laboratory model, resulting monocytes migrated to the degenerating brain cells that lacked the gene for beta-galactosidase. These cells took in the enzyme released by the monocytes and used it to break down excess GM1, thus correcting the potentially fatal buildup of this molecule.

The monocytes homed in on the brain by following a trail of signaling molecules that were released by cells adjacent to the degenerating neurons, according to Alessandra d'Azzo, Ph.D., a member of the St. Jude department of Genetics and Tumor Cell Biology. Such signaling proteins are called chemokines. Under a disease condition, these brain cells, called astrocytes and microglia, release chemokines
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Contact: Kelly Perry
kelly.perry@stjude.org
901-495-3306
St. Jude Children's Research Hospital
22-Jun-2005


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