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Lampreys look like something nightmares are made of. And they have long, eel-like bodies and big, circular mouths with several rings of horribly pointy teeth.

These things also lack a jaw and don’t have complex, true vertebrae, but they are fish — they just don’t look super fishy to us. Still, let’s not judge a book by its cover. Because on the inside, lamprey immune systems are also a little different than those of their jawed, vertebrate cousins — and that might be great news.

In fact, researchers think this difference may hold the key to developing a new way to treat human brain diseases. Lampreys are one of only two living members of the jawless vertebrate superclass Agnatha. These fish are directly descended from the first primitive vertebrates that wandered the oceans 400 million years ago, and their features haven’t changed much since then — including their immune systems.

Lampreys have a completely different acquired immune system than jawed creatures like us. We have white blood cells called B cells that send out antibodies to neutralize threats. But lampreys get rid of the middleman: Their white blood cells attack invaders directly.

When they encounter a target, these cells make little surface proteins called variable lymphocyte receptors, or VLRs for short. In a way, VLRs are similar to vertebrate antibodies, but they have a unique structure and composition that makes them arguably more useful. These proteins are shaped like horseshoes, and in the middle of the horseshoe is a binding site that attaches to pathogens.

But the key is, that binding site can be rearranged and customized depending on what it’s targeting. So overall, VLRs have a very specific immune response to invaders. And because of their horseshoe shape, they can also bind to pathogens really tightly.

Researchers have found that because of these differences — and because of how old they are,. VLRs can recognize and respond to invaders that vertebrate antibodies can’t. And while that’s awesome for lampreys, this could really help us, too.

After all, if VLRs are so good at attaching to specific targets… maybe we could get them to attach to things we’re interested in. And maybe, with a little clever engineering, we could even get them to deliver medicine to specific parts of the body. Well, in a study published in 2019 in Science Advances, researchers figured out how to do just that.

At least, in mice. In the paper, researchers looked into using VLRs to treat a kind of incurable brain cancer. This type of disease makes the barrier between the brain and the rest of the body leak.

And when that happens, those leaks expose parts of the extracellular matrix. This is a tangled web of proteins and sugars that surrounds brain cells, and it’s kind of a big deal. It helps connect neurons and tell brain cells how to do their jobs.  But when this matrix becomes exposed to the rest of the body — like in cases of brain cancer — things circulating around out there can disrupt it and break down the vital connections it’s making in the brain.

Now, here’s the cool thing: The researchers believed they could get lamprey VLRs to deliver drugs to these specific, exposed sections of the brain. And the path they took to test that was very clever. First, they injected lampreys with bits of the extracellular matrix from mice brains.

And the lampreys’ immune systems did what they do best: They made specific VLRs in response to this foreign substance. Next, the scientists isolated one of the VLRs that had attached to the matrix, and they linked it to a chemotherapy drug called doxorubicin. And finally, they injected this mixture into actual mice with brain cancer.  In the end, the VLRs did exactly what scientists wanted: They got into the mice, saw some extracellular matrix out in the wild, and went, “Oh, hey, that’s the thing I’m supposed to bind to!” And when they attached to that matrix, they delivered the chemo drug directly to the mice’s brains — and nowhere else, meaning that toxic drug only went where it was supposed to.

Oh, and, important note: The mice that got this type of treatment had significantly better survival rates than mice receiving other therapies.   Now, this was only one experiment with mice, but researchers see a lot of potential in this type of therapy for humans. It would be especially important for cancer treatments, because current options like chemo and radiation attack both cancerous and healthy cells. That’s why they have such bad side effects.

But researchers think this new method could also be used on other types of brain diseases, like Alzheimer’s and MS — since those things also make the blood-brain barrier leak. We’d just need to connect these lamprey VLRs with drugs used to treat those illnesses. There’s even talk of one day linking VLRs with probes for brain scanners, which could help detect other types of blood-brain barrier disruptions.

So, really, lampreys’ immune systems are the gift that keeps on giving. They’re paving the way to more effective treatments for multiple diseases, and someday, we might have these animals to thank for a lot of saved lives. That’s a whole lot of impact for what at first seems like just an unusual fish!  Thanks for watching this episode of SciShow Psych.

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