Hormone Might Reverse Alzheimer’s and Stroke

“We found a unique approach for delivering drugs to the brain,” says William A. Banks, professor of geriatrics and pharmacological and physiological science. “We are turning off the guardian that is 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, and blocks all. “The problem in treating a lot of diseases of the central nervous system is that we cannot get drugs past the blood-brain barrier and into the brain,” says Banks.

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 that evicts PACAP27. Then they designed an antisense, a specific molecule that turned off the impediment. “We went after the guard and essentially told him to go on break for a while so PACAP27 could get into the brain,” Banks says.

They used mouse models of Alzheimer’s disease and stroke to test what would happen if PACAP27 could get into the brain. “We reversed the symptoms of the illnesses,” Banks says. “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.”

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.

MEDICA.de; Source: Saint Louis University Medical Center