Once of the biggest dilemmas in neuroscience may just have been solved with an amazing breakthrough by a group of researchers at Cornell University – finding the way to get past the blood-brain barrier. For over 100 years scientists have been trying to get past the guards that block entry to the brain cells so therapy can be administered to stop diseases like multiple sclerosis, brain cancer and Alzheimer’s disease. That barrier may just have been crashed!
The blood-brain barrier is made up of specialized cells in the brain’s blood vessels. They act as guards that selectively prevent substances from entering the blood and the brain. Only essential molecules and nutrients like oxygen, amino acids, glucose, water has been allowed in. The guards were so good at their job that getting anything else through was impossible, until now.
A molecule naturally produced by the body, Adenosine, has been found by researchers to unlock the gate for a very short time in order to allow large brain molecules to enter. The researchers found that when adenosine receptors are activated in cells that make up the barrier to brain the gateway is opened to allow medication to be let in. Although the research has only been conducted on mice so far, the same adenosine receptors are also found in humans.
Even more exciting, an adenosine-based drug called Lexiscan, that has been approved by the FDA and has been successfully used in heart imaging on very ill patients, has been found to briefly open the gates across the blood-brain barrier and allowed to enter.
The findings appeared in the Sept. 14 edition of the Journal of Neuroscience and were funded by the National Institutes of Health. Former postdoctoral associate in Bynoe’s lab, Aaron Carman, was the paper’s lead author. “The biggest hurdle for every neurological disease is that we are unable to treat these diseases because we cannot deliver drugs into the brain,” said associate professor of immunology at Cornell’s College of Veterinary Medicine, Margaret Bynoe.
“Big pharmaceutical companies have been trying for 100 years to find out how to traverse the blood-brain barrier and still keep patients alive,” said Bynoe, who along with her colleagues have patented the findings and will be involved in pre-clinical trials and drug testing through their newly formed company, Adenios Inc.
According to Bynoe, researchers have tried to get across the barrier by modifying drugs so they would bind to the receptors, or letting them ride “piggyback” on other molecules, but without success. “Utilizing adenosine receptors seems to be a more generalized gateway across the barrier,” she added. “We are capitalizing on that mechanism to open and close the gateway when we want to.”
Researchers were able to successfully transport molecules and detrains into the brain, as well as deliver an anti-beta amyloid antibody across the blood-brain barrier, and see it bind to beta-amyloid plaque that causes Alzheimer’s in mice. “We wanted to see the extent to which we could get large molecules in and whether there was a restriction on size,” Bynoe said.
Similar work has been started for the treatment of multiple sclerosis. Researchers want to see if they were to tighten the barrier, rather than open it, would this prevent destructive immune cells from entering and causing disease.
Many drugs and proteins are known to block the signaling of adenosine receptors in mice, so future work on humans will try to identify these drugs. The researchers also plan to see if they are able to get brain cancer drugs through the blood-brain barrier, and learn more about the physiology behind how adenosine receptors regulate and guard the blood-brain barrier.
This is Ron White, two-time USA Memory Champion , memory training expert, and memory keynote speaker. I am very encouraged with this new development that could allow scientists to administer drugs to break up the plaque that causes Alzheimer’s as well as help to find ways to treat brain cancer and MS.
Source:
Science Daily – Breaching the Blood-Brain Barrier: Finding May Permit Drug Delivery to the Brain for Alzheimer’s, Multiple Sclerosis and Brain Cancers (September 13, 2011) : http://www.sciencedaily.com/releases/2011/09/110913172631.htm