Stem cells for studying neurodegeneration - Dr Kevin Eggan

Kevin - It's sort of like rebooting the identity of a cell. What people discovered - and when I say people really, it's an interesting scientist in Japan named Shinya Yamanaka -  He discovered that if you take skin cell and you force it to express a small group of genes that are at the heart of what make an embryonic stem cell an embryonic stem cell, you can convert those simple and lowly skin cells into the equivalent of an embryonic stem cell. And then we can use those induced pluripotent stem cells to make all the different cell types in the body and they're remarkable because they're sort of supercharged stem cells. They can grow forever in the tissue culture dish in the laboratory and they have the capacity to make all the different cell types in the body.

Kat - This sounds absolutely incredible - almost the stuff of science fiction! You can turn cells into any sort of cells you want. What are some of the applications of this sort of technology?

Kevin - Well, as I implied earlier, I would say that the application that people think the most about is that we would use these cells to replace those that are damaged in disease or through injury, and I think that's a very exciting area of research which is moving forward rapidly. The idea that we would make insulin producing cells from these stem cells and maybe administer them to diabetic patients or to produce transplants for people who have Parkinson's disease, there's a lot of excitement over that. Now, our own particular interest is actually in motor neuron disease as it's known here in the UK or amyotrophic lateral sclerosis, or Lou Gehrig's disease as it's known in the United States. And in this case, it's a very specific type of nerve cell which is dying, the nerve cells which connect our brains to our musculature, but unfortunately, those cells die all over the body. And so, it's difficult to think about transplanting all of these different nerve cells and having them reconnect appropriately.

So we take a different kind of approach. We've actually discovered a different sort of utility for those cells and it's really one that tries to leverage or take advantage of these remarkable new developments in human genetics that are unfolding today. And that it's that instead of making the cells which are lost in the disease to put them back, we're using them to understand why it is that they get sick in the first place and to try to stop them from getting sick or prevent the disease from progressing in people that have the disease.

And then what we've discovered is that even though people with motor neuron disease may not be outwardly sick until maybe they're in their 40s, 50s, 60s, there's probably something in many cases which is wrong with their so-called motor neurons from the very beginning. And we've been able to get some insight into those differences now and we think that there will be good opportunity for developing new drugs to stop the disease.

Kat - Do you think there might also be ways to identify people who would be at risk of developing this disease too?

Kevin - Yes, absolutely. So this is one thing that is interesting about motor neuron disease is that only a fraction of people who walk into the clinic with this disorder really are familiar with it because it's in their family. And so, one thing we're trying to discover is, in those people that don't have a clear familial history, is there some more complicated genetic makeup of them that makes them more susceptible to disease.

And by making their motor nerve cells and comparing them to individuals which have more clearly inherited forms, we're starting to get some insight into that and in fact, it does seem that at least some people with motor neuron disease have what I would call 'unappreciated heritability'. That is to say that there are disease genes running within them and they didn't necessarily appreciate it.

Kat - And you mentioned that there may be approaches for new treatments. What's in the pipeline?

Kevin - One important discovery that we've made using this type of system is that - which is quite surprising - is that other cell types in the nervous system begin to attack the motor neurons in this disease. That is to say that the problems that are going wrong in the disease aren't only limited to the nerve cells themselves but that other cells in the nervous system that are usually supportive of motor neurons seem to turn on them and attack them.

And we and others have been - over the last couple of years - very focused on the pathways which seem to be involved in this sort of motor neuron murder, this sort of terrorism against motor neurons in the nervous system, and we've been able to identify several compounds which seem to interrupt this toxic effect and at least are showing some promise in the animal models now. And so, I still think I'd caution that this is a way from clinical trials, but I think it's another new drug target which hasn't been appreciated for this disease that surely is going to be interrogated.

And in general, I would say, although motor neuron disease is devastating as all too many diseases are, and although it's a disease that for the time being, there aren't promising therapies, there are quite a lot of exciting developments in clinical development for motor neuron disease today. And so, I think there is a great deal of hope for patients for the future.