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).

 

New ALS review article available

ammar2.jpgLast week, The New England Journal of Medicine (NEJM) published a review article by Professors Ammar Al-Chalabi and Robert Brown, in which they looked at the up to date evidence on the incidence of ALS, pathological mechanisms of the disease, as well as genetics and therapeutic strategies.

We would very much like to thank the NEJM who kindly allowed us to share full text of this article on our website – this is now available to view here.

Closing the door on toxic proteins – new clues in understanding a genetic form of MND

The defects in the C9orf72 gene are known to cause motor neurone disease, but researchers don’t understand why. Defective copies of this gene are passed down in some families affected by the rare, inherited form of MND. This week MND Association grantees Drs Guillaume Hautbergue, Lydia Castelli and colleagues, based at the Sheffield Institute of Translational Neuroscience have published their research study providing some important clues about the toxicity of C9orf72. Their research is published in the prestigious journal Nature Communications. Continue reading

Life of an MND researcher – part 2: PhD edition

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.

In our previous article we introduced four MND researchers who gave us an insight what a typical day in the life of a researcher looks like and what carrying out a research study actually involves. In this continuation article, you will get the chance to look into the lives of four PhD students, who give us an overview of their projects and their usual daily duties. Continue reading

Edaravone – a month on since the FDA announcement

It’s been over a month since the announcement by the FDA of their decision to licence edaravone / Radicava for people with MND in the USA. The speed of the FDA’s decision took the drug company MT Pharma and the MND research community by suprise. It is encouraging that edaravone has been licenced to treat MND after two decades of failed drug trials. Since the FDA announcement the effects of the drug and what it means for people with MND has been extensively discussed and some of the trial data has been published.

This blog is an update on what studies have been done on edaravone and the likelihood of people with MND noticing a beneficial effect if they were to receive it. Continue reading

Collaborating to find treatment for MND

21 June – MND Awareness Day

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. 

It is at the heart of the Association to fight MND by funding and promoting research into understanding the disease so that we can defeat it. However, we would not be able to fight this battle on our own and the support of various people is crucial to defeat this MND monster.

Everyone working in the field of MND research has one aim – to find what causes this disease and find a treatment to cure it. We have already written about the long elaborate process behind developing and licensing new drugs but we have not yet talked about the people who are essential for this process to run successfully. Continue reading

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

How is tissue donation helping us to solve the MND puzzle?

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.

Last year, I wrote about our trip to a brain bank. Here, we learned about how people can arrange to donate their tissue (brain and spinal cord) to tissue banks after they die, and how it is stored and used in MND research all around the UK.

What you might be asking is: what can tissue actually tell us about MND, and how will this help us find new treatments?

To find new drugs that can beat this disease we first need to understand what is going on in the brain, which is very difficult to study in living people. This is why post-mortem tissue from people with MND is an invaluable resource. Below are four reasons why tissue donation is so important. Continue reading

Stem cells and MND

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.

In this blog I’ve chosen to write about two examples of how stem cells are used in MND research – one example from a stem cell therapy clinical trial and the other example from how stem cells are used in the lab. Before explaining these in more detail, I felt it would be helpful to have a brief introduction to stem cells – and signpost you to other sources of information along the way.

Introducing stem cells
Stem cells are basic cells that have the potential to grow into any cell type – whether that’s heart cells or liver cells, muscle or motor neurones. Another way of putting it is that stem cells are cells that don’t know what they want to be when they grow up. To realise their potential and to convert themselves into other cell types, stem cells need triggers from the body – or chemicals added in the lab – that push them towards becoming more specialised cells. Continue reading