Tag Archives: blood brain barrier

Potential Revolutionnary Treatment For Alzheimer’s

Leaky capillaries in the brain portend early onset of Alzheimer’s disease as they signal cognitive impairment before hallmark toxic proteins appear, new USC research shows. The findings, which appear in Nature Medicine, could help with earlier diagnosis and suggest new targets for drugs that could slow or prevent the onset of the disease.

The number of Americans with Alzheimer’s is expected to more than double to about 14 million in 40 years, according to the Centers for Disease Control and Prevention. Five Alzheimer’s drugs are approved by the U.S. Food and Drug Administration to temporarily help with memory and thinking problems, but none treats the underlying cause of the disease or slow its progression. Researchers believe that successful treatment will eventually involve a combination of drugs aimed at multiple targets.

USC’s five-year study, which involved 161 older adults, showed that people with the worst memory problems also had the most leakage in their brain’s blood vessels — regardless of whether abnormal proteins amyloid and tau were present.

This image depicts a blood vessel in the brain that has become leaky, or permeable.

The fact that we’re seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process,” said senior author Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. “That was surprising that this blood-brain barrier breakdown is occurring independently.”

In healthy brains, the cells that make up blood vessels fit together so tightly they form a barrier that keeps stray cells, pathogens, metals and other unhealthy substances from reaching brain tissue. Scientists call this the blood-brain barrier. In some aging brains, the seams between cells loosen, and the blood vessels become permeable.

If the blood-brain barrier is not working properly, then there is the potential for damage,” said co-author Arthur Toga, director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. “It suggests the vessels aren’t properly providing the nutrients and blood flow that the neurons need. And you have the possibility of toxic proteins getting in.

Participants in the study had their memory and thinking ability assessed through a series of tasks and tests, resulting in measures of cognitive function and a “clinical dementia rating score.” Individuals diagnosed with disorders that might account for cognitive impairment were excluded. The researchers used neuroimaging and cerebral spinal fluid analysis to measure the permeability, or leakiness, of capillaries serving the brain’s hippocampus, and found a strong correlation between impairment and leakage.

“The results were really kind of eye-opening,” said first author Daniel Nation, an assistant professor of psychology at the USC Dornsife College of Letters, Arts and Sciences. “It didn’t matter whether people had amyloid or tau pathology; they still had cognitive impairment.”

Source: https://news.usc.edu/

How To Deliver Drug Deep In The Brain

By learning how rabies virus travels in the brain, Anti-Parkinson’s drug can be delivered deep in the brain where currently the drugs are not able to reachRabies virus has the capability to trick the nervous system and cross the blood brain barrier. This trick could be used for drug design. Glycoprotein 29 present on the rabies virus is attached to a nanoparticle stuffed full of deferoxamine ( Anti-Parkinson’s medication) and injected into the brain to trick the brain.

Rabies virus may have some tricks to bypass the blood brain barrier, this trick can be used to treat disease that require drugs to effectively cross the blood brain barrier, finds a new study.

The researchers can now exploit rabies viruses machinery to deliver a Parkinson’s disease medication directly to the brain. Upon injection the nanoparticles grab excess iron and relieve symptoms. While the common cause of Parkinson’s disease is unknown, it has been proved that accumulation of iron in neurons is one of the commonest features of Parkinson’s disease.

Deferoxamine is a metal-grabbing compound and sop up the excess iron in patients. But a large quantity of this drug needs to reach the brain in order for them work.
To usher deferoxamine into the brain, the researchers Yan-Zhong Chang, Xin Lou, Guangjun Nie took advantage of a key part of the rabies virusGlycoprotein 29.
When they injected this iron-grabbing nanoparticles into mouse models of Parkinson’s disease, the iron levels dropped and this reduced brain damage caused by Parkinson’s disease.

The findings of this study is published in the ACS Nano journal.

Source: https://www.acs.org/