These projects aim to test the effectiveness of potential treatments. They aim to test potential treatments from the laboratory stage to the clinical trial environment. Read the latest news on developing treatments on our MND Research blog.
An asterisk (‘*’) next to a title marks the research projects that directly involve animals.
Principal investigator: Dr Richard Mead
Associated researchers: Prof Dame Pam Shaw and Amy Keerie
Institution: University of Sheffield
Award: £125,000 (Total amount: £250,000)
Start date: May 2014
End date: April 2018
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. Dr Mead hopes to develop our understanding of MND through mouse models of the disease and to transfer this knowledge to develop new therapies. Dr Mead is also moving into cell therapy to test a stem cell treatment in this mouse model with a leading stem cell company.
Update: To date Dr Mead has identified a new mouse model of MND, based on defects in the TDP-43 protein. He is currently using this mouse model to test a potential compound. The next steps will be to screen over 300,000 compounds and develop new therapies in collaboration with chemists at Sheffield and with the pharmaceutical company AstraZeneca.
Principal investigator: Prof Marcus Rattray
Associated researchers: Dr David Hicks, Dr Ritchie Williamson and Dr Laura Cross
Institution: University of Bradford
Start date: August 2015
End date: August 2018
Deposits of the protein TDP-43 that are found within the motor neurones in the majority of cases of MND are considered a pathological hallmark of the disease. The events that cause TDP-43 proteins to deposit within the motor neurones are currently unknown. In previous research, activation of the Unfolded Protein Response (UPR) causes the protein TDP-43 to form abnormal deposits within motor neurones. This project will aim to identify what pathways link the UPR and TDP-43 deposition within the motor neurones and whether reversing the accumulation of TDP-43 has an effect on slowing the progression of MND. The researchers will then aim to screen hundreds of compounds that may potentially reverse this process.
Associated researchers: Dr Tennore Ramesh, Prof Dame Pam Shaw and Dr Giada Cellot
Institutions: University of Leicester and University of Sheffield
Start date: November 2015
End date: October 2018
Previous research in humans and zebrafish has shown that before symptoms arise in MND, early changes occur in the interneurones (the cells linking the upper and lower motor neurones). Using zebrafish, this project will investigate if the early defects that occur in interneurones can be targeted as a potential treatment for MND, in order to slow, or even prevent, the onset of symptoms. These studies will be conducted looking specifically at the electrical activity of the interneurones.
Principal investigator: Dr Guillaume Hautbergue
Associated researchers: Dr Lydia Castelli
Institution: University of Sheffield
Start date: August 2016
End date: July 2018
Cells within our body contain a number of separated compartments, each carrying out specific functions. The blueprint for making up thousands of proteins is housed in the form of genes, in a compartment in the centre of the cell, the nucleus. A copy of the blueprint is created for each protein and is transported into the ‘open plan’ part of the cell, known as the cytoplasm. These copies serve as individual instruction manuals for the building of each protein. The copies are known as RNA. Damage to the C9orf72 gene is the commonest cause of inherited MND. The toxicity of the C9orf72 gene is linked to the transport system between the nucleus and the cytoplasm of the motor neurone. Researchers have recently found that a protein called SRSF1/F2 can help reduce this toxicity. In this project, the researchers hope to confirm the role of SRSF1/F2 in the C9orf72 form of MND in fly and human models of the disease. They will also investigate how it might be possible to reduce SRSF1/F2 safely as a possible treatment option.
Associated researchers: Dr Claudia Rebosio
Institutions: Universita di Genova and University of Sheffield
Start date: January 2017
End date: December 2018
Many researchers around the world are investigating the potential of stem cells as a therapy for MND, however, its benefits are not proven. We know that a particular type of stem cell, the mesenchymal stem cell (MSCs), found in the bone marrow, have shown beneficial effects in mice with MND. However, it is unclear how MSCs are beneficial. We know that little ‘packets’, or compartments, of MSCs known as exosomes break off from the MSCs. Within these packets are chemicals that affect the role of support cells around motor neurones. Professor Bonanno and colleagues will investigate whether these exosomes have a beneficial effect in MND on their own, in mice and human cell models of MND. This could have important implications for future stem cell trials.
Associated researchers: Prof Chris Shaw
Institution: King’s College London
Start date: March 2018
End date: February 2021
Dr Chen’s previous work has shown that by increasing levels of the heat shock protein (HSF1), the tendency of the TDP-43 protein to clump together, accumulate and cause death of motor neurones decreases. HSF1 was already found to be reduced in spinal cords of people with MND, suggesting that lack of HSF1 contributes to accumulation of TDP-43. In the current project, Dr Chen will apply a specialised gene therapy technique in a mouse model to investigate the effectiveness of increasing HSF1 levels on reducing disease symptoms. The findings could lead to identification of new drugs that might act on HSF1, giving rise to a potential treatment.
Principal investigator: Prof Nigel Leigh
Institution: University of Sussex
Start date: September 2016
End date: August 2019
The Modifying Immune Response and Outcomes in Amyotrophic Lateral Sclerosis (MIROCALS) study will aim to investigate interleukin-2 as a potential treatment for MND. Interleukin-2 has been used for many years to treat cancer, however, at low doses it is much safer but still effective against a number of immune diseases. Because the immune system is thought to be involved in causing damage in MND, the researchers believe it may be beneficial in treating MND too. This study aims to recruit 216 people living with MND in the UK and France.
Principal investigator: Dr Barney Bryson
Associated researchers: Prof Linda Greensmith and Prof Giampietro Schiavo
Institution: University College London
Start date: August 2017
End date: July 2002
The cause of muscle weakness in MND is caused by the disruption of the connections between a motor neurone and a muscle. This project will use stem cells from mice that were transformed into motor neurones and use these to create new muscle-neurone connections. These will be implanted back into the mice and observed for how well the neurones connect with muscles (innervation). The researchers will then identify the chemicals that promote successful innervation that could potentially be used in developing new therapies, focused on preventing the breakdown of muscle-neurone connections. Moreover, this study has the potential to contribute to the development of a new therapy based on replacing damaged motor neurones and restoring lost muscle function.
Principal investigator: Prof Kevin Talbot
Associated researchers: Prof Mathew Wood and Chaitra Sathyaprakash (PhD student)
PhD student: Chaitra Sathayprakash
Institution: University of Oxford
Start date: July 2016
End date: June 2019
Understanding how the C9ORF72 gene mutation leads to MND by damaging nerve cells is vital for developing potential new treatments. The Talbot group has generated motor neurones with the C9ORF72 mutation using groundbreaking induced pluripotent stem cell (iPSC) technology. They have been working on a targeted method to alter the RNA made from the C9ORF72 gene, using short stretches of molecules, known as antisense oligonucleotides (ASOs). They plan to study the effect of ASOs on their cell lines using a new technique called TRAP (translating ribosome affinity purification). The team will compare the effects of the ASOs on the C9ORF72 iPSC cells with those originating from healthy people and also with a third set of cells in which the C9ORF72 mutation has been ‘cut out’. By testing the effects of different ASO molecules on the cells, they will find out if this is a potential therapeutic strategy for MND.
Last updated: 1 October 2017