We arrived in Florida yesterday evening. This morning it was a case of getting to know where everything is – I can tell that we are going to be getting our daily exercise just by walking from one end of the hotel to the other! As the day gradually warmed up I resisted the pull of soaking up some sun (having left the UK with forecasts of yet more snow… !) and attended some of the talks at the International Alliance of ALS/MND Associations “Ask the experts” session.
The talk I was really keen to hear was Nicholas Boulis’ presentation on “Spinal cord surgery of ALS – human neural stem cell transplantation”. Dr Boulis is a neurosurgeon who has worked in the field of ALS/MND for seventeen years. He has spent this time developing techniques for spinal cord surgery. He had a fantastic, easy to understand presentation style, which made it so much easier for the audience to understand the technical details he was describing.
There are many different types of stem cells that exist – ranging from embryonic stem cells right through to endogenous stem cells. Embryonic stem cells are the stem cells that can turn into literally any cell in the body. On the other end of the scale endogenous stem cells are stem cells that exist in the adult body that are dormant. Dr Boulis gave an eloquent description of each type, explaining that at the moment ALS research is concentrating on pluripotent cells (in the middle of the two types of stem cell described above) – cells that have decided roughly which tissue they are going to turn into, but not specific to the cell types within that tissue. Hence the title of his talk – using neural stem cells, stem cells that know that they are going to turn into neurons of one type or another.
There have been a number of studies conducted in rat models of ALS that show the potential of stem cells to treat the disease. However, Dr Boulis commented that these studies reflected the honeymoon of stem cell research into MND. “As we move from taking things that work well in the rat to humans, the honeymoon period is coming to an end and things will start to get sticky” he commented. “ It’s going to be a long haul. Right now we are trying to prove that the stem cells are not dangerous, rather than be able to show that they are beneficial”.
Dr Boulis talked about some of the pitfalls to look out for during stem cell surgery. For example, it is important to avoid applying too much pressure to the spinal cord, to be careful of the volume of fluid that is injected and the speed of the injection. These are exactly the type of things that Dr Boulis has been studying to get it right. He described a fascinating series of experiments conducted in pigs. The studies began by using microelectrodes to work out exactly where in the spinal cord the needle should be injected. I learnt that the human spinal cord is 6mm long and 8mm wide. The area that stem cell surgery should target is 2mm square. He talked about designing the mechanical apparatus that holds the syringe, to the need for a flexible syringe. Again, more fascinating facts – did you know that the spinal cord moves when you breathe and when your heart beats? Hence the need for a flexible syringe, to move with the cord.
After perfecting the techniques in pigs, the next step was to try these techniques in humans. The Neuralstem trial investigating the safety of giving stem cells into the spinal cord is currently underway in the USA. The study was designed as a ‘risk escalation’ rather than a ‘dose escalation’ that would be the basis of a drug safety study. The first group of patients were not able to walk and received injections of stem cells in one side of the spinal cord only; the next group were not able to walk but had stem cells injected into both sides of the spinal cord. He explained that these patients had some pain, but that this was transitory and the longest period of pain was three weeks. The next group of patients are those that can walk before the surgery – this is the current status of the study. Two patients have taken part so far, having had stem cells injected into one side of the spinal cord only. Both patients have walked out of the hospital after the surgery. For those wanting to know even more technical detail, when he said ‘one side’ he meant five injections of 10 microlitres each (to give you an idea of scale, a teaspoon can hold 5,000 microlitres). He explained that the Neuralstem study would be following the participants for life. At the end of the study, the lessons learned will pave the way for many stem cell studies currently in the pipeline. They may also have a wider application for delivering more conventional drugs too.
I thoroughly enjoyed this presentation and I learnt a lot! Roll on the Symposium to feed my enthusiasm for learning more about how we are all striving towards a world free of MND.
A note: pluripotent is the ability to become any tissue type, while multipotent is the ability to become a variant within a tissue type.