GL Brown Prize Lecture: Professor Dame Pamela Shaw of the University of Sheffield - “Tackling the pathophysiology of motor neuron disease (MND): a translational neuroscience approach”

15 November 2019

University of York, York, United Kingdom

About the GL Brown Prize Lecture:

In 1975 The Physiological Society established the GL Brown Prize Lecture in his memory; this is an annual series of peripatetic lectures aimed to stimulate an interest in physiology. Subject to the agreement of the Editorial Board, this lecture is published in Experimental Physiology. 

2019 Lecture overview:

“Tackling the pathophysiology of motor neuron disease (MND): a translational neuroscience approach”

Motor neuron disease (MND) is one of the 3 commonest adult onset neurodegenerative disorders with a prevalence of approximately 6-8/100,000.  The clinical features are caused by injury and cell death usually of both upper motor neurons in the brain and lower motor neuron groups in the brainstem and spinal cord.  Death in most patients results from neuromuscular respiratory failure.  The rapidity of disease progression in many cases causes MND to be regarded as one of the most feared diseases in medicine.  The heterogeneity and complexity of MND has poses a challenge for neuroprotective therapy development. This lecture will cover 5 areas of topical interest in relation to this neurodegenerative condition.  

  1. An introduction to the intricate and fascinating properties of the human motor system and what goes wrong to cause the clinical and pathological features of MND.
  2. A discussion on current thinking in relation to disease pathogenesis ie why motor neurons die.  New generation genetic sequencing techologies have enable rapid progress in unravelling genetic causes of motor neuron degeneration.  Insights into disease pathophysiology arising from study of experimental models of MND will be discussed, including our ability now to reprogamme skin cells do create a human model of MND in the laboratory.  Pathophysiological changes at cellular and in vivo in rodent models and human patients will be highlighted.
  3. New scientific approaches that can be applied to the problem of MND will be considered.  These include laser capture microdissection to isolate motor neurons and study their properties in great detail.  In addition, the repertoire of cellular gene and protein expression of motor neurons in health and disease states, can be studied using transcriptomic and proteomic approaches respectively.  The other new approach is to investigate the contribution of the “neighbourhood” cells in the nervous system eg astrocytes in the initiation and/or propagation of motor neuron injury.  4.  The next section of this presentation will consider whether we are winning in terms of the translation of recent scientific research into benefits for patients who develop MND.  Progress in neuroprotective therapy development, including gene therapy approaches and in improving life expectancy and quality of life by advances in symptom management will be considered.   5. The final section will consider how the relationships between scientific researchers and patients, the public and society are changing and the positive value emerging from this two-way relationship.  Two illustrative examples include the creation of SITraN and the development of a new, recently marketed device for neuromuscular disorders.  

Biography:

Professor Dame Pamela  Shaw, Professor of Neurology and Vice President and Pro-Vice Chancellor for the Faculty of Medicine, Dentistry and Health at the University of Sheffield and Founding Director of the Sheffield Institute for Translational Neuroscience (SITraN), one of the world leading centers for motor neuron disease (MND) research.  

Professor Shaw graduated in Medicine with 1st Class Honours from the University of Newcastle in 1979. She undertook her MRCP and Specialist Training in Neurology training in Newcastle. In 1988 she was awarded an MD with commendation for her work on the neurological complications of coronary bypass surgery.

After an intermediate fellowship award from the Wellcome Trust, she was awarded a Wellcome Senior Fellowship in Clinical Science which she held from 1991 to 2001, underpinning her program of work investigating molecular mechanisms of motor neuron injury and new therapeutic approaches in motor neuron disease. 

In 1997 she was appointed Professor of Neurological Medicine at the University of Newcastle and in 2000 was appointed as Professor of Neurology at the University of Sheffield. As an undergraduate in Newcastle she was awarded the Stephen Scott; Gibb; Mary Gordon; Mona McNaughton and Phillipson Prizes/Scholarships.

Recent post-graduate awards include: Association of British Neurologists Sir Charles Symonds award (1991; 1996; 2001); American Academy of Neurology Sheila Essey award 2001; UK Royal College of Physicians Jean Hunter award 2006; the International ALS/MND Forbes Norris award 2007; Fellowship of the Academy of Medical Sciences 2007. In 2014 she was awarded the Dame Commander of the Order of the British Empire (DBE) for services to Neuroscience in the HM the Queen’s New Year’s Honours.

She has authored more than 440 publications of original research (Google Scholar H-index 92), reviews and book chapters and has edited several books on ALS/MND.  Her research is funded by the Medical Research Council, the Wellcome Trust, NIHR, the MND Association, the European Union and biotechnology & pharmaceutical industry partners. Since 1983 she has generated more than £60m in research income. 

From 2008 – 2015 she led the Clinical Studies Group for ALS/MND within the NIHR Dementia and Neurodegenerative Diseases (DeNDRoN) clinical research network which links 21 MND Care and Research Centres and has developed a network of 10 UK centres experienced in MND clinical trials. Prof. Shaw has taken part in more than 20 MND clinical trials, including roles as UK Chief Investigator and Steering Committee member  and also including several academic led studies.  She is an active member of the European Network for the Cure of ALS (ENCALS).  

If you are interested in attending this lecture and have any queries, please contact meetings@physoc.org.

Dame Pamela Shaw