Multiple sclerosis (MS) is a chronic disease of the brain and the spinal cord. It affects the insulating layers that wrap the nerve cells (the myelin sheath), and, as a consequence, disrupts nerve signals within the brain.
Symptoms vary greatly between individuals, depending on which areas of the brain are affected, and include problems with vision, sensation, memory and movement.
Around 2.5M people worldwide have MS. That said, the global disease distribution is very patchy, and Northern Europe has a much higher incidence than southern countries. Scotland has the highest number of MS cases per capita in the world, and there are pockets such as Aberdeen, Shetland and Orkney, where the numbers are up to four times higher than in England and Wales.
MS is often described as an inflammatory problem that results in damage to the myelin sheath. However, the disease mechanisms are far more complex and multifaceted; both inflammation and neurodegeneration (nerve cell death) occur, together with scarring (sclerosis) and activation of tissue repair systems. Due to this complexity, the pattern of MS activity varies between individuals, either following a steady course of deterioration (progressive forms) or being characterised by acute deteriorations that are called relapses, which are interspersed with periods of recovery (relapsing-remitting forms). Most patients with relapsing-remitting disease convert to slowly progressive symptoms later in life. The chance of relapses in MS can now be reduced by using anti-inflammatory treatments. However, progressive symptoms are due to degeneration of the underlying nerves, which have lost their myelin sheaths, and there are no treatments available to slow, stop or reverse their progress.
Work at CRM
Work at CRM aims to understand how to repair the damaged myelin sheath and protect nerves so as to develop novel pharmaceutical interventions. To do this, we use cell culture, animal models and studies of human neuropathological material.
- Professor Charles ffrench-Constant studies neural stem cells and their ability to form oligodendrocytes, the cells that form the myelin insulation layer. The aim of his laboratory is to find ways to activate neural stem cells in the brain, so that they move to the area that has been damaged and repair the myelin layer. In order to do so, the mechanisms that regulate stem cell migration, their transformation into oligodendrocytes, and the wrapping process around the nerve cells need to be understood.
- Professor Siddharthan Chandran uses human embryonic and induced pluripotent stem cells to model aspects of “MS in a dish”. This is achieved by harnessing the power of stem cells to generate unlimited numbers of nerve cells and glia (supporting cells that include oligodendrocytes). This system can then be used to look for drugs that promote the beneficial cross-talk between glia and nerve cells to promote brain repair. His lab, in collaboration with the Baker group in London, also uses other experimental models of MS and neurodegeneration to study the interaction between inflammation, neurodegeneration and repair.
- Professor Anna Williams and her team investigate why the repair mechanisms that could potentially prevent neurodegeneration are inefficient and ultimately fail. With damaged brain regions exhibiting scar formation, projects in her lab are based on the premise that signalling molecules in these scars stop repair cells from getting to the injury site. Her lab has identified key molecules that do exactly that, and they are now investigating drugs that can remove these signals and allow the cells to move across the brain and to the damaged area to repair the myelin wrap. In her capacity of an NHS consultant neurologist, Professor Williams also runs an MS clinic at the Anne Rowling Clinic (see below).
Watch an 8 minute interview with Dr Anna Williams on the AlJazeera website and/or interview below. The Shift MS Reporters YouTube channel has many videos that might be of interest, including some on stem cell research and MS.
- Professor Anura Rambukkana uses a very novel approach: A bacterial infection can trigger mature adult cells, particularly myelinating-forming Schwann cells, to revert back to immature stem cells; thus, this constitutes a natural reprogramming technology. In the long-term, his laboratory aims to apply this technology to generate safe stem cells for therapies. They further use this system to investigate how these bacteria turn off the mature signals and turn on immature signals; finding the answers to these questions may help find the key mechanisms that are important for myelination and provide targets to develop drugs.
- Professors Chandran and ffrench-Constant are the Directors of the Anne Rowling Regenerative Neurology Clinic, a charitable University of Edinburgh clinical research facility that tightly links NHS clinicians with research. The development of detailed and long-term patient registers at the Clinic helps the translation of laboratory research into clinical trials with the ultimate goal of providing personalised medicine.