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Lifespan News – Gene Therapy for Regeneration

Zebrafish genes have effects in mammals.

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On this episode of Lifespan News, Emmett Short discusses how gene therapy might be able to give people real regenerative abilities akin to zebrafish.

Script

Some animals, like zebrafish, can regenerate their body, their brain, retina, spinal cords, heart, and other complex tissues. And soon we might be able to. It got me thinking Wolverine’s don’t regenerate. Why aren’t there any superheroes based on zebrafish? So, I got our graphics team to mock up a few. Oh. OH! Uh. Uh huh. Yikes. Ok. Nevermind. Yeah I get it now.

Welcome to Lifespan News. I’m Emmett Short. Today we’re talking about gene therapy to create meta-humans. Why? Because it’s a Tuesday and that’s what we do here. The journal Cell Stem Cell, and yes that is a name weird name, has published a study about animals that have been given the zebrafish-like ability to restore their heart muscle after injury. This is screaming origin story. If a fishy-smelling vigilante starts solving crimes at Sea World, we know where to look.

According to the paper, you don’t want genes responsible for regeneration stuck in the on position. That’s how you get tumors. In zebrafish, these genes are controlled by TREEs. Tissue Regeneration Enhancer Elements. TREEs only turn on regenerative genes when they sense an injury.

Heart tissue does not normally regenerate in adult mammals, but you are going to love this. In two similar experiments researchers genetically engineered mice to express TREEs in a way that would show visual indicators only during injury response, and it worked. In uninjured mice, there was no gene expression, but in the injured mice, the TREE indicator was clearly visible.

The best part? It worked whether the injection was given before or immediately after the injury. So, if this was a therapy, it could conceivably be given after a heart attack or what have you.

Similar results were seen in pigs. They didn’t have enough virus to infect the entire pig, so they just injected the pigs’ hearts. Look, I get it, these are tough economic times. I’ve stopped shopping at Whole Foods guys. And I damn sure am not injecting an entire pig’s body when I can get the same information with a much smaller dosage. There is absolutely no reason to go hog wild.

The point is even with just treating the heart they got similar results to the mice. The indicators were only visible at the injury sites. So we’ve got targeting down.

Now, the final experiments involved a molecule called Yap. There is a pun there and I’m going to pass it up because I respect you. Yap is a transcriptional cofactor that causes rapid cell growth and division when overexpressed. Without a TREE, genetically modifying animals to express Yap in the heart kills them within days due to cardiac muscle overgrowth.

But with this new TREE method, things were much different in the final test: restoring heart function. Using TREEs to control Yap expression, they were able to restore core metrics of cardiac function. This occurred whether the injection was given before or immediately after the injury, and it provided improvements in function over an injured control group. Yap was only expressed during injuries and only at injury sites, basically it turned off after the injury was healed. Incredible. I could have used this during a few tough breakups.

This is a proof-of-principle study showing that tissue regeneration and gene therapy is a plausible and effective approach in animal models. While this is not yet a human clinical trial, it is a significant step towards one and has the potential to become the standard of care for treating heart attacks or other conditions that cause significant tissue damage. Imagine regrowing limbs, severed spinal cords, or turning the clock back on your entire body.

This is exciting stuff, and when there’s more to share, we’ll have it for you here – so make sure to subscribe and click the bell so you can stay up to date on aging research. I’m Emmett Short, and we’ll see you next time on Lifespan News!

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