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Crossing the Line: Technique could treat brain diseases
Patrick Barry

For the first time, scientists have selectively ferried a drug across the blood-brain barrier to treat a neurological disease in mice. The new method could eventually make new treatments possible for a wide range of brain disorders, such as Alzheimer's disease.

The walls of capillaries that carry blood into the brain control whether molecules larger than a few hundred atoms, such as antibodies and proteins, can pass into the spaces between neurons. This capillary barrier can stymie doctors' efforts to cure neurological diseases because most medicines can't get through.

However, some viruses, including rabies, have molecules that trick the barrier into allowing them to pass. Researchers attached a molecule from the rabies virus to a drug and found that the coupled molecules got through the capillary walls and into the brain. A drug delivered in this way kept 80 percent of mice infected with Japanese encephalitis alive for at least 30 days, while all of the experiment's untreated mice died, the scientists report online and in an upcoming Nature.

"I think the potential [of this technique] is enormous," says Manjunath Swamy, senior researcher for the group at the Immune Disease Institute at Harvard Medical School in Boston.

The molecule from the rabies virus acts as a key that corresponds to keyhole molecules on the surfaces of the capillary walls. When a key nestles into a keyhole—called a nicotinic acetylcholine receptor—the key molecule triggers a poorly understood process that moves it through the wall, carrying the drug with it.

"This [research] has enormous ramifications for many neurological-disease categories," comments Robert H. Brown, a neurologist at the Massachusetts General Hospital in Boston. The drug molecule used by the researchers is a kind of RNA that can block the activity of a gene. These RNAs, called short-interfering RNAs (siRNAs), can be custom tailored to target virtually any disease-causing gene or protein. Scientists are developing siRNAs to treat Alzheimer's, Huntington's, and Parkinson's diseases, among others.

Currently, the only way to get an siRNA into a mouse's brain is by direct injection. Other techniques for overcoming the blood-brain barrier exist, but they involve opening the barrier to all large molecules in the blood, not just the desired drug molecules.

Many questions remain before the new technique can be used on people, scientists say, such as whether some regions of the brain receive more of the drug than others and whether a person's immune system might eventually neutralize the rabies molecule.

http://www.sciencenews.org/articles/20070623/fob1.asp

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