Lamprey molecules squirm into the brain to deliver cancer drugs
With a mouth like a whirlpool full of teeth, the lamprey is not something you'd normally want anywhere near your brain. But now, researchers from the Universities of Texas and Wisconsin-Madison have used molecules taken from the freaky fish's immune system to deliver drugs inside the body – and even managed to sneak them into the brain.
The immune system as we know it is unique to mammals, but other kinds of animals use similar systems to protect themselves from infection. Instead of producing antibodies like humans, lampreys use small defensive molecules, and now it turns out that these might be useful for human therapies too.
When used in medicines, these molecules have been found to target the extracellular matrix, a mesh of connective tissue that supports, surrounds and feeds cells. If they're loaded up with drugs, they'll deliver that payload straight to the extracellular matrix, where they can accumulate and potentially have a stronger effect then being taken into cells directly.
"Similar to water soaking into a sponge, the lamprey molecules will potentially accumulate much more of the drug in the abundant matrix around cells compared to specific delivery to cells," says John Kuo, an author of the study.
But there's one place that even these lamprey molecules can't get into – the brain. That's because this most vital of organs walls itself off behind the blood-brain barrier. While that's good for protecting the brain from potential pathogens circulating in the bloodstream, it's not so good for getting medicines in to help treat brain diseases or cancers.
Previous studies have tried to pry open the blood-brain barrier with ultrasound pulses or bee venom peptides, but the new study suggests a much simpler method. Brain tumors and Alzheimer's have been found to make that barrier "leaky," which could not only allow the drug-laden molecules to pass through, but concentrate them in the spot that needs treatment.
"Molecules like this normally couldn't ferry cargo into the brain, but anywhere there's a blood-brain barrier disruption, they can deliver drugs right to the site of pathology," says Eric Shusta, an author of the study.
To test the idea, the researchers loaded the lamprey molecules with an FDA-approved chemotherapy drug called doxorubicin. These were then administered to mice with glioblastoma, a dangerous form of brain cancer, and sure enough, the treatment significantly extended the lifespan of mice, compared to a control group.
Side effects should be kept to a minimum too. In the mouse studies, the team noted that the molecules circulated through the body without accumulating in healthy brain tissue or other organs.
The researchers say the lamprey molecules could essentially be used with other drugs, including immunotherapy agents. And cancer might not be alone on the hit list – other brain diseases could be targets, if they cause disruptions in the blood-brain barrier.
The research was published in the journal Science Advances.
Source: University of Wisconsin-Madison