Barrier to Treatment For Alzheimer’s and Other Brain Disorders May Be Broken

For over 100 years scientists have been puzzled over how to cross the barriers the brain puts up to deliver therapy that could fight, and maybe even stop diseases like Alzheimer’s, multiple sclerosis, brain cancer and other neurological diseases. Now, researchers at Cornell University believe they may have solved the mystery.

Adenosine, a molecule naturally produced by the body, has been found by researchers to change the entrance way to large brain molecules. They have found that when adenosine receptors are activated in cells that make up the barrier to brain the gateway is opened to allow medication or therapy to be given.

The research was conducted on mice, but the scientists involved say the same adenosine receptors are found in the human brain as well. The 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 — so only essential nutrients like oxygen, amino acids, glucose, water and necessary molecules are allowed in. Until now, the guards were so good at their job that getting anything else through that would help was impossible.

A adenosine-based drug called Lexiscan, that has been used in heart imaging on very ill patients, and been approved by the FDA, has been found to briefly open the gates across the blood-brain barrier and been allowed to enter.

“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. 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.

“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 transport molecules and detrains into the brain, as well as deliver an anti-beta amyloid antibody across the blood-brain barrier, and were able to 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 to see if they were to tighten the barrier, rather than open it, would this prevent destructive immune cells from entering and causing disease, for the treatment of multiple sclerosis.

There are many known drugs and proteins that can block the signaling of adenosine receptors in mice, and 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.

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.

From the desk of Ron White

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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) :

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