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In the Future: A Nasal Spray to Treat Alzheimer's?

Perhaps the most obstructing barrier to treating neurological conditions is quite literally a barrier.

This post originally appeared in the Newton blog on RealClearScience. You can read the original here


A host of debilitating disorders of the central nervous system cry out for treatment. Diseases like Huntington's, Parkinson's, and Alzheimer's -- colloquially known as "The Long Goodbye" -- come prominently to mind. All exact torturous tolls, both physical and mental, on the afflicted and their families. Nobody should have to endure them.

But imagine, one day, if Alzheimer's or Parkinson's could be treated with a simple nasal spray. Wouldn't that be incredible? Well, that's just what Cobi Heijnen, a professor of neuroimmunology at the M.D. Anderson Cancer Center at the University of Texas, hopes to accomplish, using ubiquitous, often-overlooked bubble-like organelles present in almost all kinds of cells: exosomes.

Perhaps the most obstructing barrier to treating neurological conditions is quite literally a barrier. Tightly packed endothelial cells with restrictive junctions separate the body's circulatingblood from the brain's extracellular fluid. This blood-brain barrier is a decidedly good thing, as it seals off our precious brains from common bacterial infections. However, like the overprotective father that blindly regards all of his daughter's boyfriends as devilish miscreants, the blood-brain barrier frequently thwarts the delivery of many beneficial diagnostic and therapeutic agents to the brain, making it exceedingly difficult to treat neurological ailments.

Enter exosomes. In 2010, cellular biologists at the University of Alabama introduced exosomes into the nasal passages of mice. When inserted, the exosomes were capable of crossing the blood-brain barrier and reaching the neuronal cells of the mice' brains. Even more impressive, the researchers showed that exosomes can be made to ferry anti-inflammatory drugs, which diffused very rapidly after entering the brain.

"If development of exosomes as a carrier system will be pursued, it could generate a valuable strategy for treatment of CNS diseases that were previously considered as untreatable," Heijnen says.

This is really cool! But wait, it get's more exciting.

Mesenchymal stem cells (MSC), which can differentiate into a variety of cell types, are currently being developed to regenerate damaged tissues in the lungs and other parts of the body, and there's a new theory on the horizon that their exosomes can impart similar regenerative effects. This has born out in a few preliminary studies. 

Heijnen thinks that MSC-derived exosomes, when delivered to the brain, could activate the built in neural stem cells (NSCs), which function to repair damaged cells and regenerate the brain after trauma.

"If this hypothesis will be proven true, it would imply a revolution in the field of regenerative medicine," Heijnen says.

exosome.jpgDoes this mean we may one day have an exosome nasal spray to treat stroke, peripheral nerve damage, or even Alzheimer's? Heijnen is cautiously hopeful.

"The great advantage of mesenchymal stem cells (and eventually exosomes) is that these strategies are not to prevent the damage but to repair the damaged brain, which allows a much longer time window to treat the patient," he told RCScience.

"The use, preparation and characterization of exosomes needs much more research, but in my view we will see it certainly happen within a decade. However, long term safety and efficacy will be crucial and the corner stones of all these investigations to repair the damaged brain via the intranasal route."

Source:  Luca Braccioli, Cindy van Velthoven, Cobi J. Heijnen (2013) Exosomes: A New Weapon to Treat the Central Nervous System. Molecular Neurobiology. DOI: 10.1007/s12035-013-8504-9

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