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Scientists are about to break the Blood Brain barrier and revolutionise healthcare

WHY THIS MATTERS IN BRIEF

Your brain is the most heavily defended organ in the human body, it’s literally impenetrable, and that’s a problem if you need to get drugs into it to kill tumours and disease …

 

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It’s tricky to get to a human brain – and that’s a problem if you want to get drugs – or even nanobots – into the brain to fight, for example, brain tumours. After all, we grew eight whole bones with the express purpose of protecting the brain from the outside. And then there’s that funky Blood-Brain Barrier – a formidable layer of cells filtering away unwanted substances from the brain, even when they try to enter through the blood stream.

 

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By getting drugs beyond the blood-brain barrier, researchers believe they could better target treatment for Alzheimer’s disease, seizures, and plenty more. So, it’s safe to say it’s been a goal.

Now, bio-engineers finally believe they’re on the brink of breaching that barrier. And they plan to use it for good.

“Our model performed better at crossing the blood-brain barrier than others and helped us identify organ-specific particles that we later validated,” Michael Mitchell, associate professor of bioengineering at the University of Pennsylvania’s School of Engineering and Applied Science, said in a statement. “It’s an exciting proof of concept that will no doubt inform novel approaches to treating conditions like traumatic brain injury, stroke, and Alzheimer’s.”

 

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The team of Penn researchers published a paper on their findings in the journal Nano Letters, which details a model that features lipid nanoparticles (LNPs) delivering messenger RNA (mRNA) beyond the blood-brain barrier in mice.

So far, the Penn team has successfully demonstrated that its plan works in the lab. Next, they hope to further test its effectiveness in various animal models.

The barrier-busting key lies in lipid packaging. Fat-soluble substances can get through the blood-brain barrier if crafted correctly, carrying with them a mix of elements such as proteins, antibodies, or mRNA. And it is that mRNA that has the team excited.

The authors write that LNP therapies, including mRNA protein replacement and gene-editing therapies, hold “great potential” for treating a variety of neurological disorders – even brain cancer and strokes.

 

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But delivering the LNPs across the blood-brain barrier is the major hurdle. To try and clear it, the team screened a library of 14 LNPs made with structurally diverse ionizable lipids and demonstrated the performance within a mouse brain. The fresh approach was able to measure how much mRNA passed through the barrier and into the central nervous system, thanks to a fluorescent system that tracked success.

“I spent months figuring out the optimal conditions for this new in vitro system,” Emily Han, Penn Ph.D. candidate and first author on the paper, said in a statement, “including which cell growth conditions and fluorescent reporters to use.”

The testing on the animal models provided the results the team had hoped for. “Seeing the brains express protein as a result of the mRNA we delivered was thrilling and confirmed we were on the right track,” Han said.

 

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The study shows that even when a LNP made it past the initial barrier, it didn’t always show up in brain cells. Other LNP were in brain cells within six hours of injection, further highlighting the importance of selecting the correct LNP for the task. “Going forward,” the team wrote wrote, “this platform could be used to screen large libraries of brain-targeted LNPs for a range of protein replacement and gene-editing applications.”

While still early, the Penn team believes that their work has real potential in directing the delivery of a variety of drugs for a range of conditions. They also believe it could be used as a framework to help cross other barriers in the body, like the blood-placental barrier or the blood-retinal barrier.

“We hope to make inroads,” Han said, “toward repairing the blood-brain barrier or target neurons damaged post-injury.”

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