Simone DiGiovanni, Imperial College in London
Simone - Well following spinal cord brain injury, nerves do not regenerate and this leads to disability which can be a really very, very severe and long lasting, potentially forever.
Chris - But when someone injures say, their fingers or their arm in a horrible accident and has a body part re-attached, they do regain sensational movement in those parts don’t they?
Simone - That is right. There's a striking difference between the capacity of the limbs for example to regenerate the nerves and the spinal cord or the brain. And we are just now beginning to understand the fundamental reasons for this striking difference. What we did is to contribute to this understanding by identifying a way we can switch on the regenerative potential in the spinal cord and in the brain by learning how the limbs for example, are able to switch on their regenerative potential.
Chris - Why do you think that the brain and spinal cord don’t regenerate naturally, given that things like arms and legs can reconnect nerve cells if they're damaged? Why is that process purposefully disabled in the central nervous system?
Simone - Well, this is a very interesting question that I get asked quite often and I do think that the main reason is because in our limbs, in our hands for example, the anatomical structure is so much more simple than what we have in the spinal cord and the brain that regeneration and regrowth can be successful while it’s actually known that partial regeneration and regrowth in the spinal in the brain can lead to side effects like pain for example. So, maybe the system is not ready to do it by itself and we had to find a good way to help it out.
Chris - So, talk us through the study in a bit more detail. What do genes turn on or off when nerve cells are injured and how does this alter or compare between nerves in your arms and legs and your spinal cord for example?
Simone - There's a group of genes so-called ‘regeneration associated genes’ which are turned on in the periphery, let’s say in the limbs, and they're not turned on in the spinal cord. What we have identified is a so-called ‘epigenetic key factor’ called pkaF which is responsible to switch on a number of these genes altogether and this is something quite special because with the one shot of gene therapy – if you allow me to say that – we can now switch on several genes which promote regrowth in their cells instead of having to do it one by one.
Chris - Again, you’ve got this molecule, this pkaF molecule which can trigger nerve cells to want to regenerate – if I'm allowed to say ‘want’ – but the point is, what makes that pkaF turn on in a nerve in your arm or your leg, but not in the spinal cord?
Simone - Yeah, there are specific signals which are transmitted from – a cut nerve for example in a leg and this signal starts what are called ‘phosphorylation cascades’, their biochemical chemical signals that tell pkaF to be turned on to promote the regeneration programme. These specific biochemical signals are silent within the spinal cord.
Chris - And you have used gene therapy to put those signals into the spinal cord and when you do that, the nerve cells there behave as though they're in an arm or leg and they try and regrow when they're injured.
Simone - It’s almost correct. Let’s say there are signals that activate this gene called pkaF which in turn activates regeneration programme. We, by gene therapy delivered pkaF which is in the middle between the signalling and that we activated this gene and now, we trigger regeneration programme.
Chris - When you do this, what sort of level of regeneration or repair can you get in the brain and spinal cord. Is it a clinically relevant amount? If you're an injured person who is currently paralysed by their injury, would the amount of repair or regeneration you're getting in your studies in animals actually produce a meaningful benefit to that person?
Simone - It’s an impossible question to answer. So in principle, the answer is yes, but we had to perform and we’re planning to perform specific studies to address whether this level of regeneration enhances recovery following spinal cord injury in mice and after we’ve done that, we can transfer that into humans, in patients.
Chris - Simone, thank you very much. That’s Simone DiGiovanni who is from Imperial College in London and he published that study in the last week or so, in Nature Communications.