A research institute dedicated to motor neuron disease (MND)
Building a research institute dedicated to finding treatments for motor neuron disease (MND) was a fantastic challenge and would not have been possible with all our supporters who still make a big difference to our research every day. The last five years have been very exciting and have seen SITraN rise to one of the world–leading centres for research into MND.
Experts from all over the world have joined us in the fight against this devastating disease and, as neurodegenerative diseases share common mechanisms that cause nerve cells to die, we study not only MND but also have teams working on Alzheimer’s, Parkinson’s and related disorders to find further clues to advance our understanding. Breakthroughs made in one disease area can thus benefit the research into other related diseases and particularly our research into MND.
|SITraN - a research institute dedicated to finding treatments for |
motor neuron disease (MND) and related disorders
Major Challenges of MND research
MND research faces major challenges; firstly, neurons and particularly motor neurons can’t be easily studied in people or modelled in the lab and, secondly, in 9 out of 10 MND cases the cause of the disease is not yet known – this knowledge, however, is crucial to developing treatments. A major part of our research therefore still focusses on understanding the disease mechanisms at work that cause motor neurons to deteriorate and die. Today, up to 20 genes have been associated with MND, the major ones are SOD1, C9ORF72, TDP43 and FUS. We model and study these inherited mutations in the lab to find clues on how to target the disease.
|Understanding disease mechanisms is the key |
to new treatments
Developing models to study MND
We have specialised in generating a cell and animal models of MND, including neuronal cell lines, zebrafish and mouse models and have - based on our discovery of certain pathways and targets in the disease process - developed ways in which to assess the effectiveness of drugs in these models. Riluzole, the only drug currently available for MND patients, is used as the standard against which to measure any new treatment. We are also working with skin cells donated by patients which we can reprogram into stem cells and then turn into motor neurons or other brain cells such as glial cells. This new and exciting technology allows us now to study disease processes using human cell models growing them in the lab in 2D or 3D cultures.
|Co-culture of nerve cells (green) and star-shaped |
helper cells (astrocytes in red)
Pre-clinical drug development
We have invested in an industrial style high-throughput drug screening facility to be able to screen libraries of drugs in SITraN and to determine whether any of the drugs which have already proven safe in humans have beneficial effects in MND. This repurposing strategy could save many years of research and hundreds of millions of pounds compared to drug development from scratch. Our drug screens have already successfully produced a promising candidate for MND (S-Apomorphine), as well as a promising drug for Parkinson’s disease (UDCA). Both drugs are now being further tested at SITraN to see if they have strong enough effects in a range of our disease models to be taken forward to clinical trials.
|High-throughput drug screening at SITraN|
Another pillar of our therapy development at SITraN is our gene therapy programme. We are developing gene-based therapies for spinal muscular atrophy (SMA), a childhood form of MND, and for inherited forms of MND such as SOD1 and C9ORF72 MND. Here, the faulty gene is known and can potentially be replaced or silenced which will be as close to a cure as we can get.
|SMA gene therapy: restoring the missing SMN protein |
(red) to the cell
Advances into personalised medicine
MND is a very complex disease. We know today that more than ten cellular pathways can be affected in motor neurons from people with MND. In order to better manage the disease, predictions are that we might either need a cocktail of drugs to target several of the disease processes, or find the major switch to target all or most of them at once. It is likely that we will need to develop drugs according to certain variants of MND following a personalised medicine approach and finding the best treatments for each of the sub-groups of patients.
| Different types of MND might need different |
New Centre for Genome Translation
In order to tackle the variability in MND, we have invested in cutting edge DNA sequencing equipment that will allow us to sequence the genomes of MND patients and compare their genes to healthy individuals in order to find the disease causing genes and pathways and target them accordingly. Computational Biologist Professor Winston Hide has joined us from Harvard University in 2014 and has established a Centre for Genome Translation at SITraN along with a new Masters course to train future researchers in this field. With funding and support from the world-leading US biotech company Biogen and our partners from Project MineE, we will hopefully be able to solve the mystery of the disease causes and processes in MND in the near future.
|New Centre for Genome Translation: Making sense of our genomes|
Improving lives of people with MND
While we are waiting for more effective drugs to be available, we also have a comprehensive clinical research programme which aims to improve the care of people with MND here and now. We initiate and lead UK multi-centre studies to evaluate clinical interventions in MND; results for diaphragm pacing (DiPALS) and gastrostomy feeding (Progas) in MND have been published this year in the prestigious journal Lancet Neurology. Among the new technologies developed and trialled at SITraN is a customisable neck collar specifically designed for MND patients to alleviate the problems with posture, communication and eating caused by weak neck muscles. The innovative collar developed in a collaboration between SITraN, NIHR, Devices4Dignity, Sheffield Hallam University and Sheffield Teaching Hospitals with support from the MND Association has just received a UK patent this month.
|An innovative neck collar for people with MND|
New technologies for people with MND
We have also developed a new web resource for people living with non-invasive ventilation www.mymnd.org.uk/myNIV and a telehealth system (TiM) for people with MND that allows the specialist care team to monitor MND patients at home and ensures that patients have access to specialist care when and as they need it and not just at their 2-monthly clinic appointments. Crucial input and support for our research comes from our Sheffield MND research advisory group www.smndrag.co.uk, the first and only public and patient involvement (PPI) group for MND in the UK whose members are actively shaping research at SITraN to ensure the greatest benefit for people with MND.
|MyNIV - a web resource with infos, practical tips and videos |
for people using non-invasive ventilation in MND
Diagnosing MND earlier
Early diagnosis is another priority in the fight against MND. By the time MND symptoms occur, more than half of the motor neurons have already deteriorated. From the onset of symptoms until finally a diagnosis of MND is made usually another year has gone by. It is crucial therefore that we find biomarkers that allow us to recognise the disease early and to determine at an early stage whether neuroprotective treatments are having beneficial effects. As part of our diagnostic tools discovery programme we are investigating blood and cerebrospinal fluid samples to find critical markers for MND, as well as using advanced neuroimaging techniques to see how muscle composition can be used to monitor the course of MND.
|The Muscle Energy Study|
5 years on....
...we have put all the components, expertise and cutting-edge technologies here at SITraN in place to tackle MND from multiple fronts. Moreover, we collaborate with the MND research community worldwide to make sure that our joint efforts will deliver tangible benefits for people with MND.
We hope that the next five years will be equally successful and see a number of promising therapy developments in MND and that SITraN will play a big part in this. We are immensely grateful to our research funders and loyal supporters who made SITraN a reality and keep us focused on our goal - to defeat this devastating disease!
By the SITraN team
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