11th Lady Edith Wolfson Clinical Fellowship awarded

We are delighted to announce that Dr Arpan Mehta has been appointed as our latest Lady Edith Wolfson Fellow, jointly funded by the MND Association and Medical Research Council.  This clinical research training fellowship will help to launch his career as an aspiring academic neurologist, providing comprehensive training in cellular, molecular and bioinformatics technologies in a world-class environment.

Arpan is a neurology registrar in Oxford, who is taking time out from his clinical training to undertake his PhD in Edinburgh.  His project, supervised by Professors Siddharthan Chandran and Giles Hardingham at The University of Edinburgh, examines the most common known genetic mutation in motor neurone disease (MND), the C9orf72 mutation.  Arpan will exploit the recent advances in patient-derived stem cell modelling and gene editing to better understand the molecular mechanisms underlying MND.

Each motor neurone has both a cell body and neurites.  The latter are specialised projections, the longest of which are called axons that make physical and electrical contact with neighbouring cells.  Arpan’s project, focused on understanding the reasons behind changes to the axon in MND, is stimulated by encouraging data from animal models of MND, showing that targeting the axon leads to delayed onset of disease and prolonged survival.  Patient-derived stem cell modelling provides an ideal platform for Arpan’s project.

Dr Arpan mehtaArpan said: “I am extremely grateful and honoured to have been awarded this generous fellowship, enabling me to undertake research using the latest technologies in such a vibrant regenerative neuroscience environment that is in Edinburgh.

“I look forward to sharing the details of my PhD journey with the MND Association community as time progresses!”

Arpan’s research in Edinburgh will benefit from the closely linked clinical and laboratory research networks of the Anne Rowling Regenerative Neurology Clinic, Euan MacDonald Centre for MND Research and the UK Dementia Research Institute at The University of Edinburgh.

Shining a light on our non-clinical fellow: Using blue light to control muscle movement

The MND Association is proud to support the brightest minds of MND research. Outside of general healthcare and biomedical project grants that are usually awarded to senior researchers, we also offer opportunities to young researchers – these take the form of PhD studentships and fellowships.

Fellowships are awarded to post-doctoral researchers who are able to support a research project as the leading investigator. Depending on their qualifications, the fellowship can either be clinical (for healthcare professionals) or non-clinical (for researchers with purely academic background). In the last round of non-clinical fellowship applications in October 2016, the MND Association awarded a senior fellowship to Dr Barney Bryson of University College London. In his upcoming project, due to start in August 2017, he will follow up on the findings he found together with his team, led by Prof Linda Greensmith.

Using light to move muscles

The idea behind Dr Bryson’s innovative project is that we can use a stimulator that emits light to create electrical signals in motor neurones (that form connections with affected muscles), rather than attempting to create long nerve connections between the muscles and the spinal cord.

We could think of this as creating a new electrical circuit from a power supply to an electric motor after lots of the wires have been damaged. Instead of reconstructing the long wires from the power supply to the motor, the researchers can directly plug in a new device that is capable of controlling the motor (or muscle in their case).

How can we use light to move muscles?

To control muscle movement by blue light, the researchers first had to create specially-modified stem cells from mice, from which specialized motor neurones could be generated. These motor neurones produce a specific neurotrophic factor and a gene that is sensitive to light, which enables them to survive longer after their implantation, and their activity to be controlled using pulses of light, respectively.

After these cells had been constructed, they were implanted into damaged sciatic nerves (one of the nerves controlling movements of the leg) in mice. Due to the survival-promoting neurotrophic factor, the implanted motor neurones were able to establish strong connections (innervation) with an atrophied muscle. Once innervated, an optical stimulator was then used to activate the transplanted motor neurons, creating electrical impulses that directly led to contraction of the connected muscles. They are now using a sophisticated implantable optical stimulator that was developed by Prof Ada Poon at Stanford University (Montgomery et al., 2015).

Optical stimulator implant (£1 coin for scale)

Optical stimulator implant (£1 coin for scale)

 How will this work be followed up now?

Much work still remains to be done before this approach could work effectively in human patients, which is a major focus of Dr Bryson’s fellowship project. Specifically, he will investigate how to best promote innervation of muscle fibres once the motor neurones are implanted. This will be done by closely observing the process of innervation in a laboratory dish and identifying the factors that promote best neurone-muscle connectivity. This part of the project is of great importance as strong connections are necessary for the muscles to receive an electrical instruction to contract.

How will this help people with MND?

While still at an early, pre-clinical stage, this project has a potentially immense impact for people with MND as it could re-establish electrical signals to the diaphragm, our main breathing muscle. When this muscle is affected, the person’s breathing ability deteriorates and an artificial way to support breathing has to be implemented (eg non-invasive ventilation). By implanting light-sensitive motor neurones to the phrenic nerve, which controls the diaphragm muscle, an optical stimulator emanating blue light could then directly control contractions of this muscle, greatly improving the person’s ability to breathe as a consequence. The hope is to also use this mechanism for peripheral muscles in order to improve person’s movement abilities.

Dr Barney Bryson

“This exciting project represents the next step in the continued development of an entirely novel strategy to overcome the progressive loss of ability to control specific muscles that occurs in MND.

“Although this future therapy is not aimed at preventing or slowing down the progressive loss of motor neurons that occurs in MND, it effectively circumvents the problem and could enable specific muscle functions and movements to be restored in an artificial manner in MND patients whose muscles have been paralysed, thus improving their quality of life.” Dr Barney Bryson

 

To find out more about MND Association-funded clinical fellowship projects, you can read about Dr James Bashford’s project investigating muscle fasciculations, or Dr Pietro Fratta’s project looking at understanding the role of RNA in MND.

Many thanks to Dr Bryson for his input and comments on this article.

To read more about the development of the optical stimulator that Dr Bryson uses, see the original research paper by Montgomery et al. (2015).

 

Life of an MND researcher: part 1

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

We all know that rigorous research is the key to finding a cure for MND. Scientists are working hard every day to find the causes of MND, developing new treatments that would help tackle the disease and also looking for new ways to improve the quality of life of people currently living with the disease. But what does it take to have research at heart of everything you do? What is the typical day in the life of a researcher and what does carrying out a research study actually involves?

We asked eight researchers to give us an idea of what their research is all about and what their typical day looks like. Read about four of them in the following blog and keep an eye out for ‘Part 2: PhD edition‘ in the next few days… Continue reading

ANXA11 – another gene closer to understanding ALS

A new research paper has been published today in the Science Translational Medicine journal, describing a new gene implicated in developing MND. What is this gene and why is it important for our fight against MND?

Although they are not the sole cause of MND, genes play a big role in someone’s probability of developing the disease. A number of such genes that make a person susceptible to developing MND have already been identified, with most of them causing the rarer, inherited form of the disease.

A new addition to a list of genes that are related to development of ALS, the most common form of MND, has been discovered by researchers from King’s College London. Dr Bradley Smith and colleagues screened genetic data of an unusually high number of people of European origin: 751 with inherited – familial – ALS (fALS) and 180 with non-inherited – sporadic – ALS (sALS). Detailed analysis of this data found that specific mutations in the ANXA11 gene are associated with around 1% of all fALS and 1.7% of all sALS cases. Continue reading

Focus on the research presented in posters in Dublin

Over 100 talks were given at this month’s International Symposium on ALS/MND in Dublin. There were also over 450 posters of research being presented too. Time in the conference programme was allocated on Wednesday and Thursday evening (day 1 and day 2 of the 3 day conference) to visit the posters – you might think that scheduled at the end of the day they would be less well attended – but not a bit of it! It was an extremely loud and buzzy part of the conference.

Below is a brief round-up of some of the posters that caught my eye. Continue reading

Using stem cell technology to understand more about how MND and FTD develop

The MND Association are funding Prof Kevin Talbot, Dr Ruxandra Dafinca (née Mutihac) and colleagues at the University of Oxford, who are investigating the link between the C9orf72 and TDP-43 genes in MND. We wrote about this research earlier in the year. As we’ve recently received their first year progress report we wanted to give you an update on what they’ve achieved. Continue reading

New fellowship to investigate muscle fasciculations

During Awareness month in June we reported on the work of Dr James Bashford at King’s College London, exploring new ways of measuring muscle fasciculations in people with MND. The results from the one year pilot study have shown a lot of promise, which has led to Dr Bashford recently being awarded a Clinical Research Training Fellowship.

A common symptom of MND is the ‘rippling’ of muscle under the skin, these are known as muscle fasciculations. Continue reading

New genetic discoveries tell us more about what causes MND – Part 2

Two sets of MND genetic results were published yesterday. One of these results was about the importance of a new gene called NEK1. The second highlighted the role of gene C21orf2 in MND – we wrote an article about this yesterday. Both sets of results were published in the prestigious journal Nature Genetics.

What are the results and what do they tell us?

Researchers found that variations in the NEK1 gene contribute to why people develop the rare, inherited form of MND. Variations in the NEK1 gene were also found to be one of the many factors that tip the balance towards why people with no family history develop MND.

NEK1 has many jobs within motor neurones including helping keeping their shape and keeping the transport system open. Future research will tell us how we can use this new finding to target drugs to stop MND. Continue reading

New genetic discoveries tell us more about what causes MND – Part 1

Today some exciting news about the genetics of MND was published in the scientific journal Nature Genetics. The results come in two research papers published in the same issue of the journal.

This blog post discusses the results of the first of these papers for which King’s College London based Professor Ammar Al-Chalabi was one of the leading researchers. A post on the second paper will follow later.

Here we’ve given an overview of what the researchers have found, what it means for people with MND and how the analysis was conducted. You can read a more detailed explanation of the research results from the King’s press release. Continue reading

How faulty proteins disrupt waste recycling and disposal inside nerve cells

Researchers from the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield have uncovered a new function of the C9orf72 protein. A paper on their work has recently been published in the EMBO Journal.

A change or mutation to the C9orf72 gene is linked to about 40% of cases of inherited MND. We also know that changes to this gene also occur in a type of dementia called frontotemporal dementia (FTD). However, the reasons behind this link have so far been unclear.

One of the main research routes towards explaining the link between the C9orf72 gene and MND is to work out the normal function of this gene. By studying the protein the gene produces, researchers can see how alterations to this protein and the processes it is involved with result in nerve cell damage in MND. Continue reading