"Chemical passports" grant Alzheimer's drugs entry to the brain
As a semi-permeable layer that protects vessels in the brain from harmful invaders, the blood-brain barrier is highly selective in what it does and doesn’t allow to pass through. This is helpful in stopping pathogens and toxins escaping the bloodstream and entering the organ, but poses a real problem when it comes to delivering drugs. A new particle that borrows chemical passports from neurotransmitters to slip through this defense could help overcome this problem, with the technique showing promise as a way of tackling Alzheimer’s and other conditions.
The unique challenge presented by the blood-brain barrier has inspired some creative solutions when it comes to getting drugs through to the brain. These have involved magnetic particles that dissipate heat when they reach the surface of the barrier, carbon nanoparticles loaded with molecules that disguise them as amino acids, and using ultrasound to prize the barrier open to deliver chemo drugs with high precision.
The new approach was developed by scientists at Tufts University, and makes use of nanoparticles that can be loaded up with payloads depending on the job at hand. The team first combined lipid molecules with certain neurotransmitters, the brain’s chemical messengers, which are known to carry a type of “chemical passport” that allows them access to the organ.
These so-called NT-lipidoids can then be loaded into the tiny nanoparticle bubbles, along with drugs, and injected intravenously. The neurotransmitters help guide the particles across the blood-brain barrier, which then fuse with cells in the brain and release their payload.
The team tested out the effectiveness of the approach through experiments on mice. In one, it was able to deliver a gene-editing protein, which the researchers actually describe as the first demonstration of genome editing in neurons delivered with intravenous injection.
Another significant outcome of the research was the promise the technique showed when it comes to Alzheimer’s disease. One hallmark of this condition is the accumulation of tau proteins in the brain, which are thought to cause damage to brain cells. By loading the particles up with a molecule called an antisense oligonucleotide, which has been shown to slow tau buildup in previous research, the team was able to reduce levels of the protein in the mice.
The researchers note that much more work is needed to explore the safety and efficacy of the approach, but they are enthused by the early signs. A big reason of that is the potential versatility of the therapy, with the particles able to be tailored to carry drugs of different types to potentially treat a range of diseases.
"It's simple, effective, and potentially broadly applicable – we can modify the container for the drug, and by adding the NT-lipidoid, it's like attaching an address label for delivery into the brain," says Feihe Ma, study co-author.
The research was published in the journal Science Advances.