To mark National Research Appreciation Day, our trustee, Professor Richard Ribchester, shares his thoughts on the progress and future of motor neuron disease (MND) research. 

MND was first identified in the mid-19th century by the French neurologist Jean-Martin Charcot. This predated the discovery that the brain was made of cells – neurons and “glial” cells – established at the turn of the 20th Century by the Spanish anatomist Santiago Ramon y Cajal.  At around the same time, the role of motor neurons in the control of reflex movements was revealed by the English physiologist Charles Sherrington. By the 1950s, English physiologists Alan Hodgkin and Andrew Huxley, and the German biophysicist Bernard Katz had established the fundamental mechanisms by which electrochemical signals are passed from motor neurons along nerve fibres to muscle fibres, causing movement.  

These historic origins illustrate the importance of hard-fought, fundamental research – which is an ongoing global activity – into what makes motor neurons tick. We now know that motor neurons contain complex networks of molecules and scaffolds of minute threads that maintain their structure and function. Gaining more knowledge of this kind continues to be essential if we are to understand how and why motor neurons normally survive and function throughout most of our lives; yet where the weaknesses and vulnerabilities lie that, if they break down, trigger degeneration and cause MND.  

Since the 1970’s the pace of research on the causes of motor neuron degeneration in MND has accelerated dramatically. For example, we now know that MND is not one disease: there are many different forms. Some are genetic, running in families. But most types of the disease have no obvious familial connection or cause and have so far eluded explanation.  

However, a major step forward in the early 2000’s was the discovery that in most forms of MND a protein molecule called “TDP43” becomes abnormally clustered in motor neurons. Current, cutting-edge fundamental research aims to understand how this transformation occurs and why it may cause motor neuron degeneration. This discovery also means there are exciting prospects for identifying drugs that prevent molecules connected to TDP43 from causing motor neuron damage.  

There has also been dramatic recent progress in treating one specific, genetic form of MND using a ‘gene therapy’ technique called ASO (“anti-sense oligonucleotides”). Treatments like this may prove successful in future for other familial forms of the disease.  

Overall, the goals of MND research, at a cell biological level, remain focused on how to protect motor neurons and prevent them from degenerating; how to promote and enhance compensatory functions of motor neurons that are still working; and, ultimately, how to produce regeneration of lost motor neurons.  

Advances in stem cell biology, especially the discovery that human skin cells can be cultured and “reprogrammed” in a dish to form motor neurons provide exciting, human-cell approaches for identifying new drugs, or repurposing drugs used normally to treat other kinds of disease. Success in the dish can then lead to tests in adaptive clinical trials, such as the MND-SMART trial supported by MND Scotland. 

One bottleneck, limiting clinical trials at present, is identification of measurable molecular “biomarkers” of MND, that would enable neurologists to make earlier diagnosis and allow the effectiveness of novel, exploratory treatments to be better measured. MND Scotland has been instrumental in supporting research in this area too, for instance at Aberdeen University, and there is capacity in other Scottish Universities and research institutes to develop further approaches to biomarker development. 

Meanwhile, other research is ongoing to improve the quality of life of those living with MND: from better methods of care aimed at improving physical and mental well-being, to the development and engineering of technological aids, such as SpeakUnique that allow people living with MND to continue to communicate with their loved ones, and others, as the disease progresses. 

I am optimistic that, with the vital support of MND Scotland and other organisations that foster MND research, significant and substantial progress will continue to be made in all these areas over the foreseeable future. 

Richard Ribchester is a Trustee of MND Scotland. As Emeritus Professor of Cellular Neuroscience at the University of Edinburgh, Richard’s career focused on the structure and function of motor neurons in health and disease. He founded the Edinburgh Motor Neuron Disease (EdMoND) research group in 2006, which later led to the establishment of the Euan MacDonald Centre for MND Research. Richard received the Delsys Prize in 2015 for his research into new ways of studying motor neurons and became an Honorary Fellow of the Physiological Society in 2020.