Part of the challenge of delivering treatments for Alzheimer’s and other diseases linked to the brain is getting past the robust defenses the brain puts in place to protect itself. Thanks to a new study, however, we now have another solution to that particular problem.
The brain’s defenses are led by the blood-brain barrier (BBB), a biological checkpoint which lets through molecules and chemicals important for its function and health, and tries to keep out anything that’s harmful or foreign. To the brain, it can seem like medical treatments fall into the latter category.
In this new research, led by a team from Oregon State University (OSU), specially designed nanoparticles just fractions of a millimeter in size were shown to pass through the BBB, and deliver their cargo to immune cells in a specific part of the brain.
“Our work presents a significant breakthrough,” says Oleh Taratula, a professor of pharmaceutics at OSU.
What’s smart about the nanoparticles is that they were loaded with carefully chosen peptides (short proteins). These were designed to unlock the BBB ‘gates’ and get through, and recognize immune cells called microglia.
The inflammation caused when microglia go into overdrive is thought to cause a lot of damage in various neurological diseases, which is why the researchers wanted to target these cells. To cross the BBB and hit microglia with drug treatments is a double victory.
In tests on mice, the researchers were able to show the effectiveness of their approach in treating a muscle-loss condition called cachexia, which can occur as a result of various types of cancer and other diseases.
For people with cancer-related cachexia, weight loss happens irrespective of any approach to eating or nutrition. It can kill up to 30 percent of the cancer patients who develop it, and the brain’s hypothalamus – a control hub packed with microglia – seems to play a key role.
“Inflammation of the hypothalamus plays a pivotal role in dysregulating those patients’ appetite and metabolism,” says Taratula. “As cachexia progresses, it significantly impacts quality of life, treatment tolerance and overall survival chances.”
For mice treated with the nanoparticle drug delivery, there was significant reversal of the cancer cachexia. Specifically, mice treated with the novel nanoparticles showed 50 percent less muscle loss from cachexia than control mice.
And while diseases such as Alzheimer’s weren’t specifically studied here, the same technique has the potential to work across many different neurological conditions where the immune system may be overreactive – including dementia.
We’re still not sure how Alzheimer’s gets started or what helps it progress, but we have some good ideas. It’s thought that immune cells including microglia aren’t defending the brain well enough, and may even be helping to drive these diseases.
“The nanoplatform’s ability to deliver therapeutics across the BBB and target microglia opens new possibilities for treating neurological conditions characterized by brain inflammation, including Alzheimer’s disease and multiple sclerosis,” says Taratula.
The research has been published in Advanced Healthcare Materials.
