Do retroviruses contribute to the common, sporadic form of MND?

New research from scientists at the American National Institute of Neurological Disorders and Stroke in Bethesda suggest that they might. In a research paper published in Science Translational Medicine yesterday, Li, Nath and colleagues proposed that sporadic MND may be linked to an endogenous retrovirus called ‘HERV-K’. So they conducted a series of experiments to investigate their ideas further.

What are endogenous retroviruses?
These are viruses that are our body’s equivalent of fossil – a left over from our evolution many thousands of years ago. Everyone has them but they are normally in an inactive state.

They are a bit like a family heirloom, lets say a vase. You might walk past the vase every day without really noticing it until one day the cat knocks it off and it smashes onto the floor in front of you.

What did the researchers do?
First, they compared brain tissue of 10 people who died from the sporadic form of MND to brain tissue of 10 people who died from Alzheimer’s Disease. They found proteins made by the virus in MND brain tissue but not in Alzheimer’s Disease brain tissue. Next, studying one of these proteins (called ‘env’) in more detail, they found it was toxic to motor neurones.

Li and colleagues then took a step back and asked ‘what triggered HERV-K to become active in the first place?’. (In other words, going back to my analogy, what caused the vase to fall on to the floor?). They found that the trigger was activation by a protein called ‘TDP-43’ – and this protein is already linked MND.

So what does this really mean?
In a comment article giving a wider perspective on the research study, Professors Bob Brown and MND Association grantee Ammar Al-Chalabi concluded:

The exciting observations of Li, Nath and colleagues will provoke further follow up studies that will illuminate the interplay between the biology of endogenous retroviruses and seemingly impenetrable neurodegenerative disorders like ALS”.

So while this study in itself might not give us the answer, its an exciting step forward in understanding the most common form of MND, that other researchers around the world will build on.

Li et al Human endogenous retrovirus-K contributes to motor neurone disease Sci Transl Med 7 307ra153 (2015)

Brown and Al-Chalabi Endogeneous retroviruses in ALS: a reawakening? Sci Transl Med 7 307fs40 (2015)

‘Dormant viruses may cause MND when awoken’ article in The Guardian

Very ‘ice’ research

The ALS #icebucketchallenge, which started in America, has now well and truly hit the UK! The social media craze has seen thousands of people getting involved in raising awareness of ‘ALS’( the most common form of MND), and funds for the Association, by placing a bucket of ice-cold water over their heads. But what happens to the donations?

The #icebucketchallenge has raised awareness of MND and has got people asking ‘what is ALS/MND?’ The donations raised will enable us to support people with MND and fund vital research. We thought we would share with you some of our ‘coolest’ research this bank holiday weekend, which the #icebucketchallenge is helping to fund:

The UK MND DNA bank (link to previous blog) freezers store DNA at a rather chilly -80°C! Now, that’s a lot colder than any #icebucketchallenge (image courtesy of CIGMR Biobank)
The UK MND DNA bank freezers store DNA at a rather chilly -80°C! Now, that’s a lot colder than any #icebucketchallenge (image courtesy of CIGMR Biobank)

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A stem cell route to the roots of MND

Nina Rzechorzek's article 'A window into brain disease is only skin deep" was shortlistedNina Rzechorzek is based at the University of Edinburgh. In 2012 Nina’s article on Prof Siddharthan Chandran’s research was shortlisted for the Access to Understanding Competition. Here she gives an update on his stem cell research.

It was a typical morning – trying to juggle experiments, trying not to make mistakes, trying hard to get results….sometimes life can be very ‘trying’ indeed… but then I’m not affected by motor neurone disease (MND) – and what a privilege it is for me to be able to rush around, to go to work and, hopefully one day, discover something that can make a difference.  I am reminded of this as I stumble out of the morning into a less ordinary afternoon – stepping away from the bench and into the world of my boss, Prof Siddharthan Chandran.Read More »

From research to medical therapy – how research has moved on in the past 40 years

Dr Ruth Standring-Cox BSc DPhil explains about her link with MND and her research experience, including how research has moved on in the past 40 years.

After successfully negotiating the “paternoster lifts” in the old Biochemistry building at Oxford University I reached the MRC Immunochemistry Unit on the 4th floor. This was 1975 and the start of my three year DPhil research project.

ruth imageThe basics of immunology

I quickly realised that we had only been taught the basics of the immune system during my biochemistry degree. I knew that lymphocytes are white blood cells with important roles in the body’s defence mechanism and there are two primary types, B lymphocytes (B-cells) and T lymphocytes (T-cells), both originating from haematopoietic (blood forming) stem cells in the bone marrow.Read More »

A research perspective on the MND Association spring conferences

Following on from Peter Bickley, Dr Ruxandra Mutihac volunteered to present her research at the Newport Spring Conference earlier this year. Here she gives an insight in to her work at Oxford and her experience of the day.

OLYMPUS DIGITAL CAMERAThis April, I had the privilege of giving the research talk of the day at the MND spring conference in Newport, Wales. I was delighted to be given the opportunity to share with people living with MND and their carers the research I am doing at Oxford University on stem cell derived motor neurones. During the day I was completely taken aback by everyone’s interest and enthusiasm on the subject.Read More »

Using induced pluripotent stem cells to further our understanding of MND

Dr Jakub Scaber from the University of Oxford is our newest Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Clinical Research Fellow. He is investigating how the newly identified C9orf72 gene causes MND in some individuals using induced pluripotent stem (iPS) cell technology.

Courtesy of Prof Chandran's laboratory, University of Edinburgh
Courtesy of Prof Chandran’s laboratory, University of Edinburgh

Researchers funded by the Association were amongst the first to create human motor neurones from donor skin cells, mimicking the signs of MND. Today, the Association is committed to funding six research projects using iPS cell technology to further our understanding of MND. This includes the recently awarded fellowship to Dr Scaber. Read more about these projects here.

Dr Scaber will be using iPS cell technology to take skin cells from someone living with the rare inherited form of MND (5 – 10% total MND cases) caused by the C9orf72 mutation. Similar to Prof Chandran’s research at the University of Edinburgh, he will then make these cells ‘forget’ what they are and turn them into motor neurones. By studying these cells in detail he aims to find out how this mutation causes MND and whether or not gene therapy can be used as a potential treatment.

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Switching the light on for MND

MND Association-funded researcher, Prof Linda Greensmith, based at University College London, together with her collaborator Dr Ivo Lieberam from Kings College London, have introduced stem cell-derived motor neurones into mice. Published in the prestigious journal Science on 4 April 2014, her research has also demonstrated that muscle function can be controlled by light.

Modelling MND

MND Researchers use a range of models to further our understanding of MND. These can be animal models, such as mice and zebrafish, or cellular models, such as induced pluripotent stem (iPS) cell-derived motor neurones (as described by Association-funded researcher, Dr Ruxandra Muthiac, during the Spring Conference in Newport on Sunday 6 April).

These models enable us to find out more about the causes of MND by studying how changes in the genes (our genetic makeup) give rise to MND. Not only this, models of MND are the essential ‘first step’ in screening potential new MND drugs before they go on to human trials.

Prof Greensmith and her team of researchers used an early stage mouse model of MND. By using this model she was able to investigate if embryonic stem cell-derived motor neurones could be successfully transplanted into mice and whether muscle function could be controlled by light.

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