Spinal injury treatment allows mice to walk again

Chemical signals that can guide regrowing nerves disconnected by a spinal injury back towards their correct targets have been used by scientists in Switzerland to make paralysed mice walk again. Around the world, about half a million people are paralysed by spinal injuries each year; and unlike injuries to nerves elsewhere in the body, spinal cord and brain nerve cells do not spontaneously regenerate to bridge the injury. Part of the reason is that a dense scar forms at the injury site, which can prevent nerves from regrowing through it; but also, these regenerating nerves may not “know” where to grow to in order to repair and reconnect the damaged neurological wiring. But now EPFL researcher Jordan Squair and his colleagues have discovered how to bridge that scar tissue, and how to switch on a signalling molecule that acts like a homing beacon to draw regenerating nerve connections towards their correct targets. Paralysed mice treated with the experimental approach all began walking again. The team got the idea from how the nervous system develops in the embryo. It’s early days, but very    exciting…

Jordan - Much of our work trying to regrow the spinal cord is based on development. It's based on the way that a human body would naturally develop. And when our nervous system starts coming into shape, there are a lot of molecules that will guide these different wires to go where they need to go. And one of the things that we've been able to figure out is one of those, call it a guidance queue. It's almost like a beacon that the wire should come over this direction and if we put that little beacon wherever we want, we can make the wires grow towards that. And that was really one of the biggest breakthroughs that we had because when we did that, we could tell them where to go. We don't have to rely on them kind of finding their way.

Chris - Talk us through the experiment then that showed that you could do that.

Jordan - A really big advance of this work, we managed to, if you think about this injury of the spinal cord, you think of it like a big scar that things can't get through. And what we managed to do before was to grow some wires through it, but nothing happened. We didn't see any improvement in walking. Every animal was still completely paralysed. And what we managed to do now was, because we figured out how to guide them, we figured out how to use these beacons to say, 'Hey, come over here.' We were able to grow things where they're supposed to grow. And when we did that, to our surprise, they all started walking again.

Chris - These are animals with injuries to their spinal cords.

Jordan - Yes.

Chris - When you say you put these beacons in, how do you do that and and where do you put the signals then, So that these disconnected nerves can see those beacons and moreover get guided by them?

Jordan - If you imagine a message starting out from your brain, and it's going to go from your brain, it's going to go down your spine and then it hits this block, this injury, this place it can't pass. Where we put these beacons is far below that and we put them little by little bit, almost like a breadcrumb trail so that the wires can keep finding them all the way along. And so what we're able to do with this is to guide these wires all the way down and they connect up with the part of the spinal cord that is going to allow you to walk.

Chris - What's the nature of the beacon signals and how do you get different bits of the spinal cord to produce them?

Jordan - What we did in these experiments is we used gene therapy. We're turning one gene on very highly, in a very specific place. The way that we do this in this work is we use viruses and so we deliver a virus into the spinal cord that creates this beacon of these, they're growth factors, to guide the wires where they need to go.

Chris - And does this work on all classes of nerve cells or are there different horses for different courses, as it were. You used different beacons to recruit and direct different classes of nerves because there are different types of nerves going both up and down the spinal cord, aren't there? Some carry sensory information, some carry movement information?

Jordan - Certainly. And we're just starting to understand how complex this is and how many different types there are. What we found in this is that there was actually a very specific kind of nerve that was going down that was very, very important for the recovery of walking. If you don't have this kind of nerve, you don't recover. And we were able to target it with this beacon. It has a way of recognising that beacon as what you would call a receptor. And so a big challenge moving forward is to catalogue all the different kinds of nerves that we have then to start to be able to regrow them where they need to go.

Chris - How do you make sure that the right nerve goes to the right place and makes the right connection and your arm signals don't end up moving your foot, for example?

Jordan - Yeah, it's a very long standing question and I think we haven't solved that here. To connect everything to the right spot is quite complicated. There's different theories about it and I think the one that I like the most that some people have shown quite nicely is that it might be that the nerves actually already know where to go. And so if we can get their wires into the right spot, they might already know who to connect to.

Chris - When you did this in your animals, I mean obviously a mouse and a rat is not a human being, but how dramatic was it and how successful was it? What was the sort of breakdown of the results?

Jordan - For us to start seeing this happen, it was really, really exciting and it was so impressive because it didn't happen overnight. It happened over the course of a couple of weeks. You started to see them move their legs and then after a couple of more weeks they started to walk again. It was a very natural process, which makes it all the more believable. It is not a magic bullet, it's not that we did something and all of a sudden, magic, everything was working. Every single mouse progressively regained the ability to walk over a period of time. That is very fitting with what we know about how long it would take.