Saint Louis University researchers have identified a way to get a potential treatment for Alzheimer's disease and stroke into the brain by facilitating its passage across the vigilant blood-brain barrier (BBB).
The scientists isolated the BBB molecule that prevents entrance of the pituitary adenylate cyclase-activating polypeptide (PACAP). This hormone acts as a general neuro-protectant, defending the brain against many types of insult and injury. They then designed an antisense to turn off the impediment.
The team reports that they were able to reverse the symptoms of the illnesses. Mice that had a version of Alzheimer's disease became smarter, and in the stroke model, the group reduced the amount of damage caused by the blockage of blood to the brain and improved brain recovery.
Simply turning off the gatekeeper molecule that kept PACAP27 out of the brain allowed enough of the hormone that already is in the body to get inside the brain. This effectively treated strokes, but the mice that had a version of Alzheimer's needed both an extra dose of PACAP27 and the antisense that turned off the gatekeeper to improve learning.
The findings are significant for three reasons, notes William A. Banks, M.D., professor of geriatrics and pharmacological and physiological science at Saint Louis University. “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.”
The results will be published in the November 12 early online issue of the Journal of Cerebral Blood Flow & Metabolism.