IMPROVED treatments for brain diseases such as Alzheimer鈥檚 and Parkinson鈥檚 may be on the cards, thanks to studies of a protein made by the bug that causes cholera. The protein seems to open the blood-brain barrier, which protects the brain from substances that might damage it. The finding may lead to new ways to get drugs into the brain.
Several years ago, while trying to develop a cholera vaccine, Alessio Fasano of the University of Maryland School of Medicine in Baltimore discovered that cholera bacteria (Vibrio cholerae) produce a toxin called zot. He found that this protein makes the wall of the small intestine more permeable by opening up the cell 鈥渏unctions鈥� that normally stop large molecules getting through the intestine walls.
Fasano went on to show in animals that this protein could make the gut absorb large molecules such as insulin. A similar human protein called zonulin had the same effect.
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To find out if these proteins also break down the blood-brain barrier, Fasano treated brain tissue samples with zot and zonulin. Sure enough, both the proteins bound to receptors in the tissue that seem to open the junctions between cells.
Now Fasano is testing whether zot-like proteins could open these cellular junctions and allow drugs to enter animal brains. 鈥淲e鈥檝e moved to animal models to see if we can modulate the blood-brain barrier,鈥� he says.
William Pardridge of the University of California in Los Angeles agrees that Fasano鈥檚 finding could lead to ways of getting drugs into the brain. 鈥淲hat he has would potentially be a new form of blood-brain barrier disruption,鈥� he says. But he questions the safety of breaching the barrier and leaving the brain exposed. He thinks it would be better to sneak drugs through using the brain鈥檚 own transport systems.