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Tuesday, 30 March, 1999, 07:40 GMT 08:40 UK
Drug 'bouncers' under the microscope
Scientists are trying to identify how drugs enter the brain
Scientists believe they have discovered why many drugs for treating brain disorders do not work.

They say a backdoor entry to the brain is blocked by two proteins which act as bouncers, throwing the drugs out.

The findings could have implications for a range of conditions which affect the nervous system, including Aids, cancer and depression.

Scientists have been working for years to discover why some drugs do not pass over a blood-brain barrier and enter the nervous system.

Brain barriers

The researchers, from Yale and Washington University Schools of Medicine, say they have identified a protein called p-glycoprotein (Pgp) at the barrier.

This collaborates with another protein to stop drugs going past a second barrier known as the choroid plexus.

The researchers believe that, if they can block both the protein bouncers, drugs such as combination therapy for Aids may be more effective.

Professor David Piwnica-Worms, of Washington University School of Medicine, said: "It might be possible to enhance delivery of many drugs by blocking the transporter proteins at the choroid plexus in a selective and careful way."

Scientists believe that HIV may hide in the brain, meaning that it can never be totally eradicated unless combination therapy can reach past the choroid plexus.

Cancer

The US scientists identified the role of Pgp and the other protein, multidrug-resistance associated protein (MRP), while studying the way cancer cells work.

Through radioactive imaging, they identified Pgp in the choroid plexus tissue.

Pgp has been known for some time to act as a transporter of many molecules across cell surfaces.

The scientists found that Pgp threw chemotherapy drugs out of the cells.

"The fact that you see the compound [chemotherapy drugs] in the choroid plexus - but not in the cerebrospinal fluid - told us there must be a barrier there holding the compound back from reaching the brain," said Professor Piwnica-Worms.

The scientists say Pgp is found on the brain side of the choroid plexus, while MRP was on the blood side.

Writing in the Proceedings of the National Academy of Sciences, the scientists say they found that Pgp stopped the cancer drug Taxol from entering the brain.

The scientists are now working to identify the exact function of the proteins.

See also:

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