Skip to main content

Drug Delivery to the Brain for Alzheimer's

Cornell University researchers may have solved a 100-year puzzle: How to safely open and close the blood-brain barrier so that therapies to treat Alzheimer's disease, multiple sclerosis and cancers of the central nervous system might effectively be delivered.

The researchers found that adenosine, a molecule produced by the body, can modulate the entry of large molecules into the brain. For the first time, the researchers discovered that when adenosine receptors are activated on cells that comprise the blood-brain barrier, a gateway into the blood-brain barrier can be established.

Although the study was done on mice, the researchers have also found adenosine receptors on these same cells in humans. They also discovered that an existing FDA-approved drug called Lexiscan, an adenosine-based drug used in heart imaging in very ill patients, can also briefly open the gateway across the blood-brain barrier.

The blood-brain barrier is composed of the specialized cells that make up the brain's blood vessels. It selectively prevents substances from entering the blood and brain, only allowing such essential molecules as amino acids, oxygen, glucose and water through. The barrier is so restrictive that researchers couldn't find a way to deliver drugs to the brain -- until now.

"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 Margaret Bynoe, associate professor of immunology at Cornell's College of Veterinary Medicine and senior author of a paper appearing Sept. 14 in the Journal of Neuroscience. Aaron Carman, a former postdoctoral associate in Bynoe's lab, is the paper's lead author. The study was funded by the National Institutes of Health.

"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 with colleagues have patented the findings and have started a company, Adenios Inc., which will be involved in drug testing and preclinical trials.

Researchers have tried to deliver drugs to the brain by modifying them so they would bind to receptors and "piggyback" onto other molecules to get across the barrier, but so far, this modification process leads to lost drug efficacy, Bynoe said.

"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."

In the paper, the researchers describe successfully transporting such macromolecules as large dextrans and antibodies into the brain. "We wanted to see the extent to which we could get large molecules in and whether there was a restriction on size," Bynoe said.

The researchers also successfully delivered an anti-beta amyloid antibody across the blood-brain barrier and observed it binding to beta-amyloid plaques that cause Alzheimer's in a transgenic mouse model. Similar work has been initiated for treating multiple sclerosis, where researchers hope to tighten the barrier rather than open it, to prevent destructive immune cells from entering and causing disease.

Although there are many known antagonists (drugs or proteins that specifically block signaling) for adenosine receptors in mice, future work will try to identify such drugs for humans.

The researchers also plan to explore delivering brain cancer drugs and better understand the physiology behind how adenosine receptors modulate the blood-brain barrier.

Aaron J. Carman, Jeffrey H. Mills, Antje Krenz, Do-Geun Kim, Margaret S. Bynoe. Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier. The Journal of Neuroscience, 2011; DOI: 10.1523/JNEUROSCI.3337-11.2011 

Comments

Post a Comment

Popular posts from this blog

Neuronal Switch to Prevent Neurodegenerative Diseases

Scientists at Northwestern University report a surprising discovery that offers a possible new route for the treatment of neurodegenerative diseases. In a study of the transparent roundworm C. elegans, they found that a genetic switch in master neurons inhibits the proper functioning of protective cell stress responses, leading to the accumulation of misfolded and damaged proteins. Neurodegenerative diseases, ranging from Huntington's and Parkinson's to amyotrophic lateral sclerosis and Alzheimer's, are believed to stem from early events that lead to an accumulation of damaged proteins in cells. Yet all animals, including humans, have an ancient and very powerful mechanism for detecting and responding to such damage, known as the heat shock response. "Why are these diseases so widespread if our cells have ways to detect and prevent damaged proteins from accumulating?" said Richard I. Morimoto, who led the research together with postdoctoral colleague Veena Prah...
Post a Comment
Read more

Dystonia Medical Research Foundation Honors Two Warren Men for Promoting Awareness of Debilitating Disease

Jason Dunn and Mike Delise recently returned from the Children & Family Dystonia Symposium in Chicago, where they were presented with Star Awards. The Dystonia Medical Research Foundation (DMRF) recognized Dunn and Delise for their efforts to promote greater public awareness of dystonia, a neurological disease. "I think this is probably the only time in my life that I am speechless," says Dunn. "I wasn't expecting this award at all." "Bringing awareness and donations to the Dystonia Medical Research Foundation is the single most important thing we can do--this is how a cure will be found," says Delise. "The people who deserve this award are all the people who have dystonia who bring awareness every minute of their life. Jason is my hero and to be able to help your hero is a thrill for me." Dunn began exhibiting unusual postures and an awkward gait at age 6. While most children this age are mastering their abilities to run, jump, and so...
Post a Comment
Read more

Human Brain Doesn't Stop Developing at Adolescence

Source: University of Alberta Faculty of Medicine & Dentistry. The human brain doesn't stop developing at adolescence, but continues well into our 20s, demonstrates recent research from the Faculty of Medicine & Dentistry at the University of Alberta.  It has been a long-held belief in medical communities that the human brain stopped developing in adolescence. But now there is evidence that this is in fact not the case, thanks to medical research conducted in the Department of Biomedical Engineering by researcher Christian Beaulieu, an Alberta Innovates -- Health Solutions scientist, and by his PhD student at the time, Catherine Lebel. Lebel recently moved to the United States to work at UCLA, where she is a post-doctoral fellow working with an expert in brain-imaging research. "This is the first long-range study, using a type of imaging that looks at brain wiring, to show that in the white matter there are still structural changes happening during young adult...
Post a Comment
Read more