"We found a unique approach for delivering drugs to the brain," says William A. Banks, M.D., professor of geriatrics and pharmacological and physiological science at Saint Louis University. "We're turning off the guardian that's keeping the drugs out of the brain."
The brain is protected by the blood-brain barrier (BBB), a gate-keeping system of cells that lets in nutrients and keeps out foreign substances. The blood-brain barrier passes no judgment on which foreign substances are trying to get into the brain to treat diseases and which are trying to do harm, so it blocks them without discrimination. "The problem in treating a lot of diseases of the central nervous system - such as Alzheimer's disease, HIV and stroke - is that we can't get drugs past the blood-brain barrier and into the brain. Our new research shows a way of getting a promising treatment for these types of devastating diseases to where they need to be to work," says Banks, who also is a staff physician at Veterans Affairs Medical Center in St. Louis.
The therapy - known as PACAP27 - is a hormone produced by the body that is a general neuro-protectant. PACAP stands for pituitary adenylate cyclase-activating polypeptide. "It is a general protector of the brain against many types of insult and injury," Banks says. He compares a specific guarding mechanism in the BBB - efflux pumps - to bouncers at exclusive nightclubs. While they welcome those on the approved guest list, they look for trouble-makers trying to crash the party, refuse to let them in and evict them if they do get in.
The scientists isolated the particular gatekeeper than evicts PACAP27. Then they designed an antisense, a specific molecule that turned off the impediment. They used mouse models of Alzheimer's disease and stroke to test what would happen if PACAP27 could get into the brain. "The mice that had a version of Alzheimer's disease became smarter and in the stroke model, we reduced the amount of damage caused by the blockage of blood to the brain and improved brain recovery. We went after the guard and essentially told him to go on break for a while so PACAP27 could get into the brain. We reversed the symptoms of the illnesses," Banks says.
Simply turning off the gatekeeper that kept PACAP27 out of the brain allowed enough of the hormone that already is in the body to get inside the brain, where it effectively treated strokes. However, the mice that had a version of Alzheimer's disease needed both an extra dose of PACAP27 and the antisense that turned off the gatekeeper to improve learning. "These findings are significant for three reasons. We have found a therapy that reverses symptoms of Alzheimers's disease and stroke in a mouse model. We have isolated the particular roadblock that keeps the treatment from getting into the brain. And we have found a way to finesse that obstacle so the medicine can get into the brain to do its work," Banks says. "This could have implications in treating many diseases of the central nervous system." http://www.medicalnewstoday.com
In search of probiotics' oral potential
UK-based Leatherhead Food International (LFI) is seeking commercial interest for a research project that will explore the potential of probiotics to deliver oral health benefits. ...http://www.nutraingredients.com
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