Su Metcalfe, The University of Cambridge
Multiple sclerosis is a chronic disease causing the nervous system to inflame, and one of the most common causes of disability in young adults. Merck Serono have awarded Su Metcalfe a million pound grant to start trials of a new, nanoparticle treatment. She explained more to Chris Smith...
Su - The disease that we’re working on is multiple sclerosis and this is where the immune cells actually attack yourself – the brain and the spinal cord. All the treatments today are involving suppressing the immune response. These are the active cells that are attacking the nerve cells. But underneath this, there's also – once the nerves are damaged, they can't be repaired.
Chris - How are you trying to tackle it with your work?
Su - We’ve prepared a natural repair factor that occurs in the body, but we’ve placed it inside a kind of magic bullet so we can target this factor to the damaged areas of the nerves. The magic bullet then releases slowly the factor that's going to repair those nerves over a period of time. So, it’s going to help repair the nerve and at the same time, it’s going to help reduce the immune response against the nerve.
Chris - If we could look at each of those things in turn then, first of all, what is the repair factor? How does that work?
Su - This is a factor called LIF or Leukaemia Inhibitory Factor which is a stem cell factor and it’s been discovered very recently that it does repair nerves.
Chris - How does it work?
Su - It’s not known, but we think it’s stopping the inflammation that's associated with damage to the nerve and allows repair cells to actually go in and recreate the functional nerve.
Chris - These stem cells are already in the brain or the part of the nervous system but they're not necessarily switched on or functional to repair the damage. You're saying you put this factor in and not only does it damp down the inflammation, but it can also stimulate those stem cells to do a repair process.
Su - That's exactly the process, yes.
Chris - And now, tell us the other aspect of what you're describing which is the magic bullet - you've got to deliver this LIF factor in somehow. How are you doing that?
Su - We’re placing the LIF factor inside the same material that if anyone has had stitches for an operation, they have these soluble stitches which gradually dissolve. So, we’re using that same material, but making the material extremely small so you get tiny, tiny particles. And we have the factor embedded in the material. On the outside, we can put a target molecule which will carry those tiny nanoparticles directly to the nerves that are damaged.
Chris - How do you get the particles to where they're needed in the body? Do you have to inject them?
Su - To start with, we’ll be injecting them. But also, we are able to take the particles through a nasal spray and they will crossover into the brain at the back of the nose. There's normally a barrier that protects the brain, but the one place there is no barrier is just behind the nose.
Chris - Once they get into the brain, how do they know where to go? How do they know where the damage is occurring because of the MS so they have to target that area or do they just go everywhere?
Su - Essentially, they will flow into the brain, but they have a sticky molecule on the surface that will recognise the places that are damaged. And so, they will then start to pile up on those damaged areas and release the factor LIF.
Chris - What is the sticky molecule that enables you to target these particles to the right place in the brain?
Su - We attach to the surface of the particles something called an antibody which is specific for only certain cells in the brain and these are the cells that can repair the damage.
Chris - So, you deliver the particle either through the nasal spray or in the blood. The antibody on the surface enables them to home in to the right place in the nervous system where the inflammation and damage is occurring. They then ooze out this LIF factor then what happens?
Su - Then the factor will act on those cells that are able to repair the nerves and cause them to switch on and start their repair.
Chris - Have you got data in people that this works?
Su - No, we haven't done it yet in people. We have done it in mice and we showed that this works.
Chris - Will you now be taking this into a clinical trial to see if you can achieve the same effect in people?
Su - The funding award is to take this into pre-clinical trials which we need to do before we can go into people and that will take about perhaps two years.