From rxpgnews.com
New method to overcome multiple drug resistant diseases developed by Stanford researchers
By Stanford University,
Aug 18, 2008 - 3:59:37 AM
Many drugs once considered Charles Atlases of the pharmaceutical realm have been reduced to the therapeutic equivalent of 97-pound weaklings as the diseases they once dispatched with ease have developed resistance to them.
The problem is well documented for antibiotics, although not confined to them. Chemotherapy drugs that were once highly effective when first used against a particular cancer now are often rendered near powerless when a patient's cancer resurges.
Even more devastating, when an organism develops resistance to one drug, it often becomes resistant to other drugs (known as multi-drug resistance), rendering not just one medication but a whole class of therapeutics useless against it.
But researchers at Stanford University have developed a method to get around one of the most common forms of resistance, thereby opening up some if not many resistant diseases to the reinvigorated fury of the medications that once laid them low. To do it, they took a tip from nature.
Nature has developed all of this firepower for getting things into cells, and one of the ways is to create entities that are arginine-rich, said Paul Wender, the Bergstrom Professor of Chemistry at Stanford University. Arginine is an amino acid, the building block of proteins, and as such is found in virtually every cell in the human body, as well as other mammalian bodies.
Using such a common transporter to ferry a potent medication inside a resistant cell is a bit like recruiting your grandmother to cart a load of switchblade knives through customs. Indeed, Wender said, Arginine-rich sequences appear to figure in the mechanisms by which many pathogens invade cells. Wender's team used a necklace of eight arginine molecules to surround the medication they worked with.
Wender and his colleagues figured out that a particular molecular subunit within arginine, called a guanidinium group, was what nature actually exploits to get foreign substances through cell membranes. Working with Taxol(r), a widely used chemotherapeutic agent, they attached a series of arginines with their associated guanidinium groups and tried it out against Taxol-resistant ovarian cancer cells implanted in mice. It worked.
It's an exciting result to be able to take a drug known to work against cancer, but stymied by resistant cells, and restore it to effectiveness using an arginine transporter, Wender said. This bodes well for use with other drugs that succumb to resistance.
A paper describing the work is scheduled to be published next week in the online Early Edition of the
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