http://www.eurasiareview.com/30062016-new-technology-could-deliver-drugs-to-brain-injuries/

New Technology Could Deliver Drugs To Brain Injuries

Schematic illustrating how intravenously injected peptide would accumulate at the site of brain injury. Credit Ryan Allen, Second Bay StudiosSchematic illustrating how intravenously injected peptide would accumulate at the site of brain injury. Credit: Ryan Allen, Second Bay Studios

A new study led by scientists at the Sanford BurnhamPrebys Medical Discovery Institute (SBP) describes atechnology that could lead to new therapeutics fortraumatic brain injuries. The discovery, published todayin Nature Communications, provides a means ofhoming drugs or nanoparticles to injured areas of thebrain.

“We have found a peptide sequence of four amino acids,cysteine, alanine, glutamine, and lysine (CAQK), thatrecognizes injured brain tissue,” said Erkki Ruoslahti,M.D., Ph.D., distinguished professor in SBP’s NCI-Designated Cancer Center and senior author of thestudy. “This peptide could be used to deliver treatments that limit the extent of damage.”

About 2.5 million people in the US sustain traumatic brain injuries each year, usually resulting from carcrashes, falls, and violence. While the initial injury cannot be repaired, the damaging effects of breakingopen brain cells and blood vessels that ensue over the following hours and days can be minimized.

“Current interventions for acute brain injury are aimed at stabilizing the patient by reducingintracranial pressure and maintaining blood flow, but there are no approved drugs to stop the cascadeof events that cause secondary injury,” said Aman Mann, Ph.D., postdoctoral researcher in Ruoslahti’slab and first author of the study.

More than one hundred compounds are currently in preclinical tests to lessen brain damage followinginjury. These candidate drugs block the events that cause secondary damage, including inflammation,high levels of free radicals, over-excitation of neurons, and signaling that leads to cell death.

“Our goal was to find an alternative to directly injecting therapeutics into the brain, which is invasiveand can add complications,” explained Ruoslahti. “Using this peptide to deliver drugs means they couldbe administered intravenously, but still reach the site of injury in sufficient quantities to have an effect.”

The CAQK peptide binds to components of the meshwork surrounding brain cells called chondroitinsulfate proteoglycans. Amounts of these large, sugar-decorated proteins increase following brain injury.

“Not only did we show that CAQK carries drug-sized molecules and nanoparticles to damaged areas inmouse models of acute brain injury, we also tested peptide binding to injured human brain samples andfound the same selectivity,” added Mann.

“This peptide could also be used to create tools to identify brain injuries, particularly mild ones, byattaching the peptide to materials that can be detected by medical imaging devices,” Ruoslahticommented. “And, because the peptide can deliver nanoparticles that can be loaded with largemolecules, it could enable enzyme or gene-silencing therapies.”

This platform technology has been licensed by a startup company, AivoCode, which was recentlyawarded a Small Business Innovation Research (SBIR) grant from the National Science Foundation forfurther development and commercialization.

Ruoslahti’s team and their collaborators are currently testing the applications of these findings usinganimal models of other central nervous system (CNS) injuries such as spinal cord injury and multiplesclerosis.

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