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Scorpion venom to probe brain cancer

Glioma, a type of brain cancer, is one of the most deadly of all cancers. For glial cells are neural stem cells and hence, unlike ordinary neurons, they can divide and migrate all over the adult brain. At present there are 24,000 new cases of glioma each year in the USA and 18,000 of those usually die in their year of diagnosis.

There is, as yet, no treatment for glioma, but at the American Association for the Advancement of Science annual conference this week, Harald Sontheimer of the University of Alabama at Birmingham, Alabama, announced an intriguing new specific probe for glioma with therapeutic possibilities.

At his company, Transmolecular Incorporate, Sontheimer is working on a constituent of the venom of the giant Israeli scorpion (Leiurus quinquestratum), which binds to and inhibits a cell component found only in glioma cells.

For glioma cells have a type of ion channel in the cell membrane that is not found in normal glial cells. These "glioma chloride channels" or GCCs, are thought to be the malignant modification that lends glioma cells their invasiveness. Chloride transport in and out of the cell through these channels also allows the cells to more efficiently take up and expel water, and hence adjust their size to slip through the narrow extracellular spaces of the brain. And the malignancy of glioma cells is indeed directly proportional to the number of GCCs in their membranes.

The constituent of scorpion venom that binds to the GCCs is a 36-amino-acid protein known as chlorotoxin. To try and reproduce its effects in a more easily mass-produced protein, Sontheimer and his colleagues have produced various synthetic chlorotoxin-like proteins, using genetically engineered E. coli as the production line.

So far, they have shown that in mice implanted with human gliomas, the synthetic chlorotoxin does accumulate in the tumors. They hope to capitalize on this property by attaching other therapeutic drugs to the toxin in order to piggyback them into the tumor cells. "At the moment we're not sure whether the chlorotoxin alone would be enough to treat the cancer, but it does seem to delay its ability to disperse," Sontheimer explained, "which would make it a useful adjunct to surgery". The group is hoping to start human clinical trials later this year.

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Abdulla, S. Scorpion venom to probe brain cancer. Nature (1999). https://doi.org/10.1038/news990204-6

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