Researchers Discover a Method to Penetrate the Blood-Brain Barrier

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Cornell researchers reveal that an existing FDA-approved drug can facilitate the delivery of other large molecules across the blood-brain barrier.

In a landmark discovery, scientists from Cornell have determined that a drug called Lexiscan (regadenoson injection) is capable of activating adenosine receptors expressed on blood-brain barrier (BBB) cells. Senior author of the study, Margaret Bynoe, associate professor in the department of microbiology and immunology in Cornell’s College of Veterinary Medicine, and Do-Geun Kim, postdoctoral associate, demonstrated in mouse models that it is possible to deliver chemotherapy drugs and other larger molecules into the brain following a course of the drug Lexiscan. The team also demonstrated that Lexiscan worked in a similar manner on the channels of human primary endothelial cells.

Typically, molecules of more than 450 daltons are prevented from crossing the BBB to protect the “complex brain physiology and strict ionic environment” of the brain, the researchers wrote in The Journal of Clinical Investigation. "We can open the BBB for a brief window of time, long enough to deliver therapies to the brain, but not too long so as to harm the brain. We hope in the future, this will be used to treat many types of neurological disorders," said Bynoe in a press release. The researchers said that the discovery could have specific implications for the treatment of Alzheimer’s disease and chemotherapy-resistant cancers that cause brain tumors such as gliomas.

Lexiscan is A2A adenosine receptor (AR) agonist that temporarily decreases expression of transporter P-glycoprotein (P-gp). P-gp is normally highly expressed on brain endothelial cells and is responsible for blocking the entry of most drugs delivered to the brain. The P-gpo protein is also expressed by many different types of cancers, making them resistant to chemotherapy. The researchers concluded, "A2A AR activation on BBB endothelial cells offers a therapeutic window that can be fine-tuned for drug delivery to the brain and has potential as a [central nervous system] drug-delivery technology."


Lexiscan was approved by FDA in 2008 as a heart-imaging agent and is manufactured by Astellas. It works by increasing blood flow through the arteries of the heart during a cardiac nuclear stress test and is used specifically for patients who are unable to exercise adequately for the stress test. It is administered prior to a radiopharmaceutical and facilitates the myocardial uptake of the imaging radionuclide.

Source: Cornell University, ScienceDaily, The Journal of Clinical Investigation