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Scientists from the Sheffield Institute for Translational Neuroscience have joined a £1.3 million research initiative to find effective treatments for Spinal Muscular Atrophy (SMA), the leading genetic cause of death in babies and toddlers. The new UK research consortium, led and funded by the SMA Trust, is the first of its kind to investigate the childhood form of Motor Neuron Disease (MND).
SMA is a debilitating disease caused by a faulty gene that affects nerve cells needed to control the muscles we use for moving, swallowing and breathing. One in 40 people are a carrier for the disease and in the most severe cases, approximately half of those affected, children rarely live beyond two years. The consortium, announced today (Tuesday 29 September 2015) during the first ever UK SMA Awareness Week, consists of world-class research and clinical experts based at the University of Sheffield’s Institute for Translational Neuroscience (SITraN) as well as Oxford, Edinburgh and London universities.
The main aims of the project are to further develop existing drug targets and identify new neuroprotective therapies to maintain function throughout the lives of people living with SMA and to identify improved ways of delivering treatments in order to maximise benefit throughout the body.
Professor Mimoun Azzouz who leads an extensive research programme on SMA at SITraN said: "This is a great initiative for SMA research in the UK. Significant progress has been made in the field, however the creation of this consortium will bring together excellent SMA experts to further our understanding of the disease and accelerate therapy development."
The SMA Trust has spent nearly £3 million since it was founded and now funds 75 per cent of all UK charity funded research into the condition. It also helped create SMA Europe, an umbrella organisation that funds research projects all over Europe and the US, as well as promoting knowledge-sharing, collaboration and representation of a united ‘patient voice’ to pharmaceutical companies and regulatory authorities involved in clinical trials.
Joanna Mitchell, CEO of The SMA Trust said: “These are exciting times in SMA research and for the new UK research consortium. Recent years have seen rapid advances, with several companies now actively pursuing clinical trials for potential treatments. Whilst a cure for SMA remains the ultimate goal, we also recognise that, for the time being, ‘success’ is equally likely to come in the form of combinations of treatments that improve the quality of life of people living with SMA.”
The potential therapies for SMA currently in clinical trials are mainly concerned with increasing the amount of a crucial protein called Survival Motor Neuron (SMN), which is depleted in various degrees in people who have SMA. This offers great promise for treating SMA if such therapies can be delivered before motor neuron loss is established. However, it is believed that the principal effect of the SMN protein on the neuromuscular system occurs early in development, meaning that increasing the levels of SMN after development has occurred may not result in a substantial benefit on motor function for the majority of people living with SMA. This becomes an increasingly important issue as due to advances in therapies which increase SMN levels, more people will be living into adulthood with SMA in the future.
The Consortium, led by Professor Kevin Talbot at Oxford University, will seek to address this problem by looking more closely at the specific mechanisms of neuromuscular failure in the disease and investigating whether influencing other ‘non-SMN’ pathways will identify potential therapies which will benefit all individuals living with SMA by maintaining and enhancing the function of surviving motor neurons.
Listen to Prof Mimoun Azzouz talking about the new UK SMA research consortium on BBC Radio Sheffield live on 29th September with Howard Pressmann. The interview starts at 01:36:50.
More than 40 researchers from across departments of The University of Sheffield and Sheffield Hallam University met on 22 September at SITraN to exchange their knowledge on glia and the role of these cells in neurological diseases. The networking event was sponsored by the Biochemical Society and brought together scientists working on a wide range of topics and approaches.
Highlights of the day: Alzheimer’s Society Research Fellow Dr Claire Garwood from SITraN reported on how impaired insulin signalling in human astrocytes is thought to contribute to dementia pointing to interesting links between diabetes and Alzheimer’s disease; Professor Matthew Holley from the Department of Biomedical Sciences presented findings from transplantation studies where glial scar tissue seems to serve as a guide for nerve cells to reach their destination; Dr Leandro Beltrachini from the Department of Electric and Electrical Engineering talked about how diffusion MRI can be used to generate in silico white matter models.
The meeting closed with a fantastic plenary talk by Professor Alexej Verkhratsky from the University of Manchester giving a comprehensive overview on the history of glia research and state of current knowledge, dispelling common myths and misconceptions.
The organisers Dr Claire Garwood from SITraN and Dr Clare Howarth from the Department of Psychology said: “Glia play a central role in neurological diseases and it is great to see that an increasing number of scientists are looking at these brain cells which seem to play a crucial role in protecting our nerve cells from damage and ultimately from diseases like Alzheimer’s disease and Motor Neurone Disease.”
A drug which has already been in use for decades to treat liver disease could be an effective treatment to slow down progression of Parkinson’s disease, scientists from the University of Sheffield have discovered.
The research led by academics from the Sheffield Institute for Translational Neuroscience (SITraN), in collaboration with scientists from the University of York, supports the fast-tracking of the drug ursodeoxycholic acid (UDCA) for a clinical trial in Parkinson’s patients.
Following the motto "EveryAugustUntilACure", SITraN PhD students Jodie Stephenson and Alejandro Lorente Pons organised a revival of last year's Ice Bucket Challenge for Motor Neurone Disease (MND), also known as Amyotrophic Lateral Sclerosis (ALS). For a small donation towards MND research, visitors to Endcliffe Park in Sheffield had a chance to drench the scientists and find out about the research into Motor Neuron Disease (MND) at SITraN, as well as the charity work of the MND Association South Yorkshire branch. The team raised more than £600 in total which will go towards MND research. The event was covered in a radio interview with Jodie, Alejandro and Ann Quinn from the MND Association South Yorkshire branch by sheffieldlive (from 7:00 –20:13 mins). For more photos visit the MND Association South Yorkshire Facebook Page. An article on the event can also be found on the MND Association website.
A pioneering trial investigating the safety and efficacy of diaphragm pacing used to alleviate breathing difficulties for people with motor neuron disease (MND), has revealed the intervention is not generally beneficial to patients.
A team of MND specialists, led by researchers from the Sheffield Institute of Translational Neuroscience (SITraN), conducted the first randomised controlled multi-centre clinical trialto assess the risks and benefits of the intervention for patients.
The diaphragm pacing device was approved for humanitarian use in MND patients in 2011 by the US Food and Drug Administration. Despite a lack of conclusive evidence for the benefits of the intervention, diaphragm pacing is now widely offered to patients with MND around the world. The device, which is similar to a heart pacemaker, sends electrical impulses to stimulate the main breathing muscles in the diaphragm.
The results of the DiPALS study, published in the journal Lancet Neurology, show that diaphragm pacing was not beneficial when used in addition to non-invasive ventilation (NIV) where slightly pressured air is delivered into the lungs through a face mask. In fact, patients who used diaphragm pacing lived on average 11 months shorter than those who used NIV alone.
Lead researcher, Dr Christopher McDermott from SITraN, who is based at the University of Sheffield, said:
“The results from the DiPALS study are incredibly disappointing, because as a researcher and an MND doctor you start out with some hope that this is a treatment that can be truly beneficial for people living with MND.
“Unfortunately, DiPALS did not show any benefits for diaphragm pacing in MND and, in fact, our study showed that it may actually be harmful. Although the results are disappointing, it was an important study to carry out as this evidence shows us that for most people there is no benefit in having diaphragm pacing and that the major surgery needed is something people living with MND should not go through.”
He added:“We carried out the DiPALS study because breathing difficulties are a major problem in MND, especially during the later stages of the disease. Current guidelines recommend non-invasive ventilation (NIV) should breathing difficulties arise, however we know that the benefits of NIV are limited and that NIV does not suit everyone. Therefore, research into complementary and alternative techniques to help with breathing is needed.
“We were aware of the work in the United States on diaphragm pacing in MND and we wanted to know if it would be beneficial for our patients. Therefore, we decided to design a randomised controlled clinical trial of diaphragm pacing in MND.
“Funding bodies like the NHS and NICE need this evidence of benefit before a treatment can be made available in the UK. Also, because it is a treatment that requires a major operation, we wanted to make sure beyond reasonable doubt that diaphragm pacing is worthwhile for patients, adding sufficient benefit such as living longer and a better quality of life.
“We established collaboration within the MND community, including the Dementia and Neurodegenerative Disease Research Network (DeNDRoN), and the MND Association and we then applied for funding from the National Institute for Health Research (NIHR)to carry out this clinical trial. By collaborating with other UK MND Care Centres we were able to carry out a well-designed clinical trial to determine if this intervention was beneficial to people living with MND.”
Dr McDermott concluded: “MND is an awful disease and affected individuals, loved ones and the health care professionals involved in providing care, are understandably always eager to consider new treatments. It is important that new treatments are evaluated in rigorous trials to demonstrate their benefit and importantly ensure no harm is done. The result from DiPALS demonstrates that the increasing “nothing to lose” approach is inappropriate and we should not lower our standards by starting treatments without clear evidence of benefit.”
“I am always humbled by the precious time and effort individuals give up to take part in our research studies. Those individuals who participated in DiPALS have contributed enormously to ensuring we understand the effects of diaphragm pacing in patients with MND and will ensure that we now put our focus and resources on developing other treatments that may help.”
This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR-HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association of England, Wales and Northern Ireland.
DiPALS Study Group (2015) Lancet Neurology. http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(15)00152-0/abstract
Podcast: Dr Chris McDemott discusses study with The Lancet’s Richard Lane http://www.thelancet.com/pb/assets/raw/Lancet/stories/audio/laneur/2015/laneur_300715.mp3
There is also a great blog published by the MND Association to explain the result further https://mndresearch.wordpress.com/
More information on related topics can be found on the MND Association website:
For more information on non-invasive ventilation in MND visit: www.mymnd.org.uk