Researchers have discovered a way to bypass the blood brain barrier, thus providing them with a way of quickly and easily delivering a hormone, which offers promise as a treatment for Alzheimer’s disease and stroke, to the brain.
The blood brain barrier (BBB) acts as a sentry protecting the brain from foreign substances, however the BBB considers drugs to be foreign substances and therefore they are also unable to pass through it. Thus, delivering therapeutic agents to specific regions of the brain presents doctors with a major challenge when trying to treat diseases of the central nervous system, such as Alzheimer’s disease and stroke. However, researchers at Saint Louis University have found a way of disarming the BBB, thus allowing therapeutic agents to gain access to the brain.
Professor William Banks and colleagues were studying a hormone called PACAP27 which acts as a neuroprotectant. However, PACAP27 is unable to pass through the BBB, so the researchers identified the component of the BBB which denies PACAP27 access – a peptide transporter, and designed an antisense molecule that switched the component off, thus enabling PACAP27 to pass through the BBB.
The researchers then experimented with mouse models of Alzheimer’s disease and stroke to determine whether enabling PACAP27 to reach the brain would affect the animals. Results showed that the hormone reversed the symptoms of both diseases. Endogenous amounts of PACAP27 were enough to reduce the amount of damage caused by stroke once it was able to gain access to the brain. The hormone also improved cognitive function in the mouse model of Alzheimer’s disease, however to do this the researchers also had to give the animals an extra dose of PACAP27.
“These findings are significant for three reasons. We have found a therapy that reverses symptoms of Alzheimer’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,” said Professor Banks in a news release. “This could have implications in treating many diseases of the central nervous system.”
Dogruko D, Kumar VB, Ryerse JS, et al. Isolation of peptide transport system-6 from brain endothelial cells: therapeutic effects with antisense inhibition in Alzheimer and stroke models. Journal of Cerebral Blood Flow & Metabolism. Advance online publication 12 November 2008; doi: 10.1038/jcbfm.2008.131
News release: Hormone Shows Promise in Reversing Alzheimer’s and Stroke. Saint Louis University Medical Center. November 10th 2008.
