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On the 16th of September, Professor Pamela Shaw (Director, Sheffield Institute for Translational Neuroscience and Professor of Neurology) hosted a delegation from King Fahad Medical City (KFMC), Riyadh, Saudi Arabia following a previous successful visit to the medical city in Riyadh in May 2012. KFMC is one of the biggest specialised hospitals in the Kingdom of Saudi Arabia, where it has a Clinical department concerned with tertiary level patient care, which offers teaching for health care students, training of medical students and residents in various medical fields, in addition to research.
The overall aim of both visits between the two institutes is to establish a collaboration from which both countries will significantly benefit. KFMC is in the process of establishing a translational neuroscience research centre as part of the National Neuroscience Institute (NNI) a regional referral centre for neurological disorders. SITraN is a world recognised centre of excellence that combines clinicians, scientists, technicians as well as students under one roof that are all dedicated to the study of neurodegenerative diseases and developing therapies that could offer better treatment options and quality of life for patients. A collaboration with Saudi Arabia offers a number of interesting opportunities to explore new clinical studies due to the high number of some clinical disorders in Saudi Arabia such as Spinal Muscular Atrophy (SMA) in children. Such studies have never been done in the Middle Eastern population and might offer new insights into specific neurological disorders adding to studies based on Caucasian populations. Linkage studies could be easily performed for the purpose of genetic hunting of certain neurological diseases in Saudi because of the culture of this country where relative marriage is a well-known tradition.
Dr Richard Mead and Professor Pamela Shaw in collaboration with AstraZeneca have won an award under the MRCs ‘Mechanisms of Disease’ call for £280,000. The project will investigate the role of the kinase, GSK-3, in animal models of MND. AstraZeneca are providing access to a compound, AZD1080, which inhibits GSK-3 and has Phase I clinical data. This compound, will be tested alone and in combination with drugs which activate the anti-oxidant Nrf2-ARE pathway in an optimised animal model. One of these drugs S[+]apomorphine, has already been identified in SITraN as a promising candidate for clinical testing and has received orphan designation from the European Medicines Agency for treatment of MND. Positive results with AZD1080 alone or in combination with S[+]apomorphine would encourage further development in patients due to the extensive clinical experience already obtained for AZD1080.
Dr Mead said: “This is as a great opportunity to leverage the drug development expertise of a major pharmaceutical company in the fight against MND. We will combine this expertise with our research strength in MND, and in particular the very robust systems we have developed for in vivo testing of potential therapies. This is a very exciting project for us and fits perfectly within the objectives of the Sheffield Institute for Translational Neuroscience”.
Dr Richard Mead, based at the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield, has been awarded the Kenneth Snowman-MND Association Lectureship in Translational Neuroscience.
The five-year Kenneth Snowman-MND Association lectureship is aimed to embed preclinical expertise in motor neurone disease (MND) models within SITraN as a national resource. Dr Richard Mead was awarded the lectureship as he has the expertise and knowledge to enable high quality pre-clinical research into MND. Dr Mead has over 14 years experience in both academia and industry with a background in models of MND (mice and fibroblasts or ‘skin cells’) and multiple sclerosis.
Developing disease models is important for furthering our understanding of MND and allows researchers to screen potential new drugs for a beneficial effect before they can be given to humans, by means of a clinical trial. As well as a track record of taking compounds into clinical development, Dr Mead hopes to use this knowledge and experience to develop MND specific therapeutic compounds. Dr Mead has already shown effectiveness of two compounds using his pre-clinical screening programme, with one being given ‘Orphan drug’ designation by the European Medicines Agency (EMA).
Professor Pam Shaw and Dr Mead have also recently been awarded one of only 15 national Medical Research Council (MRC)-AstraZeneca Compound Collaboration Grants under the MRC’s ‘Mechanisms of Disease’ call for £283,000. This project will investigate the role of the kinase, GSK-3, in animal models of MND using a compound from AstraZeneca (AZD1080), which inhibits GSK-3.
Dr Mead commented on being awarded the lectureship and what he hopes to achieve in the next five years: “I am delighted to have been awarded this prestigious lectureship; It’s a fantastic opportunity to pursue my passion, which is to bring new treatments to bear on this devastating disease. We have an ambitious strategy to stimulate preclinical research in MND through the work conducted here in SITraN but also in collaboration with Industry and others and this funding will give me the freedom to pursue this program of research.”
Director of Research Development at the MND Association, Dr Brian Dickie, commented: “We are delighted to be able to help secure the position of an outstanding young scientist at one of the top European centres for MND research. Our understanding of the causes of MND and the reasons why motor neurons degenerate is increasing rapidly and we need more researchers like Dr Mead who are ideally placed to move this new understanding from the laboratory to the clinic.”
Members of the Sheffield MND Research Advisory Group (SMND RAG) based in SITraN in the Department of Neuroscience signed the STH NHS Trust and University of Sheffield up to the MND charter. Members of the SMND RAG, Hannah Hollinger, Emily Goodall and Sarah Wyatt met with Sir Andrew Cash, Chief Executive, of the Sheffield Teaching Hospitals NHS Trust and the University of Sheffield’s Vice-Chancellor, Professor Sir Keith Burnett to talk to them about the Motor Neurone Disease Association’s MND charter which embraces the natural rights of people with MND and their carers and sets out the respect, care and support they deserve and should expect.
The MND Charter aims to gain support from individuals and organisations with a personal or professional connection to MND, in working towards the vision of the right care, in the right place, at the right time for people with MND and their carers. Anyone can sign up to the MND charter. By doing so, you are showing that you have listened to the voice of people with MND and their carers, and pledge to understand and support the principles and priorities set out in the charter. Sister Hannah Hollinger from the SMND RAG Group said “We are keen to publicise this event to raise the profile of this condition and feel that gaining support for quality of care for people with MND and their carers from key influential individuals within the healthcare field is vital to raise awareness of the rapidly changing needs of this vulnerable group of patients. They are a group of patients whose condition and needs can change rapidly and therefore need a responsive and efficient service to ensure a timely provision of care. The more that people understand this condition and its needs the better the care provision can be. The Sheffield MND Research Advisory Group based in SITraN are driven to increase awareness of Motor Neurone Disease and are aiming to approach key individuals within health care locally in Sheffield to gain support for the MND charter.”
The Motor Neurone Disease Association urge all individuals with a connection to MND, either personally or professionally, and organisations working with people with MND to endorse and sign up to the charter. By signing the charter, you are pledging your understanding and support for the charter statements to help ensure people with MND and their carers have their rights respected and are given the very best opportunity to access the care they need to live the highest quality of life possible and achieve dignity on death.
Professor Sir Keith Burnett signing up to the MND charter.
Scientists from the University of Sheffield have paved the way for new treatments for a common genetic disorder thanks to pioneering research on zebrafish – an animal capable of mending its own heart.
Charcot Marie Tooth disease (CMT) is the most common genetic disorder affecting the nervous system. More than 20,000 people in the UK suffer from CMT, which typically causes progressive weakness and long-term pain in the feet, leading to walking difficulties. There is currently no cure for CMT.
A research project conducted at the Sheffield Institute for Translational Neuroscience (SITraN) and the MRC Centre for Developmental and Biomedical Genetics (CDBG) by Dr Andrew Grierson and his team has revealed that zebrafish could hold the key to finding new therapeutic approaches to treat the condition. Dr Grierson said: "We have studied zebrafish with a genetic defect that causes CMT in humans. The fish develop normally, but once they reach adulthood they start to develop difficulties swimming. "By looking at the muscles of these fish we have discovered that the problem lies with the connections between motor neurons and muscle, which are known to be essential for walking in humans and also swimming in fish."
CMT represents a group of neurodegenerative disorders typically characterised by demyelination (CMT1), a process which causes damage to the myelin sheaths that surround our neurons, or distal axon degeneration (CMT2) of motor and sensory neurons. The distal axon is the terminal where neurotransmitter packages within neurons are docked. The majority of CMT2 cases are caused by mutations in mitofusin 2 (MFN2), which is an essential gene encoding a protein responsible for fusion of the mitochondrial outer membrane. Mitochondria are known as the cellular power plants because they generate most of the supply of adenosine triphosphate (ATP), which is used as a source of chemical energy.