Collaborating across Europe to find a cure: ENCALS 2016

332 delegates, 135 posters, 41 talks, one goal: to cure ALS

The European Network for the Cure of Amyotrophic Lateral Sclerosis (ENCALS) was set up to find a cure for ALS/MND by working collaboratively across 35 research centres (universities and hospitals) throughout Europe.

The 14th meeting of ENCALS took place in Milan between 19-21 May and was attended by scientists and doctors from across Europe. Researchers from the USA and Canada were also invited to present at this meeting.

Presentations on day one of this year’s meeting looked at some of the techniques to help identify genetic changes (mutations) linked to MND, such as whole genome sequencing. This is a rapidly growing area of research, thanks to Project MinE  – a global effort to find MND causing genes.

Clinical research was the focus on day two, and discussed the latest imaging and biomarker research. This is an important area as it will offer new ways to help track the progression of MND, and help to speed up diagnosis of this disease.

Our researchers present their work

Buchman group 1

Prof Vladimir Buchman (right) and his research group: (l-r) Dr Michail Kukharsky, Haiyan An, Tatyana Shelkovnikova

MND Association funded researcher Prof Vladimir Buchman attended ENCALS with his research group from Cardiff University. Their research uses a mouse model of MND to study the role of the FUS gene in detail and its involvement in MND.

Dr Michail Kukharsky, a post-doctoral researcher funded by us on this project presented a poster on a protein called CREST (calcium-responsive transactivator), which has been shown to interact with FUS. Prof Buchman’s PhD student Haiyan An was presented with an award for her poster on research into cell models on the effects of the FUS gene in ALS/MND.

Dr Richard Mead

Dr Richard Mead, SITraN, UK

Dr Richard Mead from the Sheffield Institute for Translational Neuroscience (SITraN) holds the Kenneth Snowman MND Association lectureship. His research involves screening potential MND drugs using a mouse model and is a member on our Biomedical Research Advisory panel, helping to review the grant applications we receive.

At the ENCALS meeting he presented on his early stage research into whether a drug recently licensed for Multiple Sclerosis could be beneficial in a mouse model of MND.

Encouraging young MND researchers

This meeting is a chance for the European ALS/MND research community to come together. As it is smaller than our International Symposium on ALS/MND, it is the perfect opportunity for young researchers to present their data, sometimes speaking for the first time at an international meeting.

Jodie Stephenson, who is supervised by Dr Mead at SITraN, gave a talk on her research into a TDP-43 mouse models of MND. This followed on from Jodie presenting a poster on her work at the International Symposium last year. She was helped in attending both ENCALS and the symposium thanks to the support of the Association’s South Yorkshire branch.

ENCALS also gives young researchers the opportunity meet with more established members of the MND research community. Making contacts with potential colleagues of the future ensures the best and brightest young researchers remain in MND research.

Ammar and Francesco Pagnini ENCALS tweetDr Francesco Pagnini, from the Catholic University of Milan, was presented with the Young Investigator award. This award is given for outstanding research in ALS by researchers under the age of 35.

Dr Pagnini is researching mindfulness and how it can be used to improve the wellbeing and quality of life of people with MND, and whether it has any impact on disease progression too. He has previously looked into how mindfulness can benefit MND caregivers also.


Collaborating to find a cure

Research into MND is a collaborative effort and does not happen in isolation. At the ENCALS meeting, researchers can take on board the latest findings in their specialist area of MND research and speak to those involved in carrying out this work. Contacts made at ENCALS can result in sharing expertise and resources across borders and laboratory benches.

Our research grants manager, Dr Sadie Vile, attended this year’s ENCALS meeting. She found it a great opportunity to thank researchers who help with peer review of the grant applications we receive twice a year (see this video for more information on peer review), as well as meet new researchers who can potentially help us with this in future.


To find out more about ENCALS visit Catch up with tweets from the meeting at #ENCALS

For more information on funding research involving animals please see our website.

Re-evaluating clinical trial guidelines for MND

To mark International Clinical Trials Day (20 May) we reflect on the ALS Clinical Trials Guidelines workshop that took place in March. The MND Association co-sponsored this successful meeting, held at Airlie House in Virginia USA. Approximately 140 delegates from across the world attended, including 11 MND researchers and doctors from the UK.

Why was this meeting held?

The meeting was a key stage in the process to update (and improve) international guidelines for clinical trials in amyotrophic lateral sclerosis (ALS, the most common form of MND).

The first international ALS clinical trials guideline workshop took place in 1998. The guidelines were designed to improve the quality of clinical trials in ALS, and provide evidence based recommendations to those designing and carrying out all stages of clinical trials.

What was discussed?

Part of the workshop looked at how clinical research studies are designed: including whether participant eligibility criteria should be restricted and how to take into account the variability of ALS (such as the possible sub-types of ALS and differences in speed of disease progression).

Clinical trials are traditionally set up in several phases or parts. Phases 1 and 2 test safety and help design the later stages of trials (such as working out the optimal dosage of the drug). Phase 3 trials test treatment effectiveness. At the workshop there was much discussion over the ideal design of phase 2 and phase 3 trials. As we learn more about the variability of MND, there is increasing likelihood that future phase 2 trials shift from their traditional purpose, and are designed to also assess the effectiveness of a trial treatment.

In the last decade there have been a long list of drugs tested in large phase 2 and 3 trials which have failed to show positive results. Looking at why these were unsuccessful, and learning lessons from them, could help in the design of future phase 3 trials.

Dr Brian Dickie, Director of Research Development at the MND Association who attended the workshop, commented on another area which was discussed:

“The use of biomarkers in clinical trials is a new area that was not really a part of the original guidelines. Potential biomarkers for diagnosing and tracking MND are currently under investigation. Including a biomarker element in future clinical trials will help us to learn more about the disease and identify participants most likely to benefit from the drug under investigation.”

Trial leaders of tomorrow

We also supported the attendance of four young UK clinician-scientists in order to provide them with an exceptional learning, networking and development opportunity. They have given us a few thoughts on the meeting and what they feel they have gained from attending this workshop.

Dr Rebecca Broad (l) and Dr Rubika Balendra (r)

Dr Rebecca Broad (l) and Dr Rubika Balendra (r)

Dr Rebecca Broad (University of Sussex, Brighton): It was a fantastic learning opportunity and has fuelled my enthusiasm to continue being involved in ALS research. It also helped me to put my own research in perspective and has sparked new ideas of ways to analyse my data. It truly felt like a landmark event in the history of ALS research.

Dr Rubika Balendra (University College London): I particularly enjoyed meeting and hearing from such a range of participants, including patients with ALS, drug regulatory agencies, statisticians, pharmaceutical companies, charities and clinical experts in MND and other disease areas. It became clear over the three days that integrating the wealth of expertise across these contributors is the key to driving research forwards.

Dr Johnathan Cooper-Knock (l) and Dr Malcolm Proudfoot (r)

Dr Johnathan Cooper-Knock (l) and Dr Malcolm Proudfoot (r)

Dr Malcolm Proudfoot (University of Oxford): The discussions at the meeting were hugely encouraging with respect to my own work (investigating the use of magnetoencephalography scans as a potential biomarker). The value added by people with ALS at every step in the formation of recommendations was also noticeable.

Dr Johnathan Cooper-Knock (University of Sheffield): Interacting with, and being part of, the global community of experts in the care for ALS patients was the definite highlight.  I have been to many scientific meetings but this was different – everybody in the room had a direct focus on the clinic and on obtaining new, effective treatments for ALS. I have an understanding of where the field needs to go in future – of what is needed to stay nimble enough to test a large number of therapies whilst maintaining the rigour to know when we have found an effective drug.

The slides and audio of the workshop are available online.

For more information on clinical trials:

Pesticides linked to increased risk of developing MND

The results from a study looking at the possible links between exposure to environmental toxins (found in pesticides) and motor neurone disease (MND) was published yesterday (9 May) in the journal JAMA Neurology.

A group of researchers from the University of Michigan, led by Dr Feng-Chiao Su and Dr Eva Feldman, have found that exposure to pesticides is associated with an increased risk of developing MND.

What did the study involve?

156 people with amyotrophic lateral sclerosis (ALS, a type of MND) and 129 healthy ‘control’ participants from Michigan, USA completed questionnaires on their occupation history, gave blood samples, or did both.

The questionnaire asked about their occupations over four windows of time; at any point during their life, in the last 10 years, in the last 10-30 years, and over 30 years ago. From their answers, the researchers worked out the likelihood of each participant’s exposure to pesticides.

The levels of 122 persistent environmental pollutants (including organochlorine pesticides or OCPs) were tested for in blood samples taken from participants.

Persistent environmental pollutants are those with a long half-life, meaning that they break down slowly. This meant that they could be tested for in the blood, even if exposure happened several years ago. However, the blood sample cannot tell us the source of the pollutants, such as if it was through work, at home or even from eating fruit and vegetables that had been sprayed with pesticides.

What do the study results say?

The results from the questionnaire indicated that exposure to pesticides at work during any point of a person’s life is linked to an increased risk of MND.

Blood samples showed that concentrations of five environmental pollutants were also associated with increased risk of developing MND.

In studies such as this, the measure of this link between the two factors is given as an odds ratio. The odds ratio represents the chances that an outcome (in this case risk of developing MND) will occur after being exposed to something (in this case pesticides). A ratio of greater than one indicates that there are higher odds of the two being associated.

The odds ratio for reported exposure at work was 5.09, whereas the odds ratio for the five chemicals in blood samples ranged from 1.81 to 5.74 (for cis-Chlordane, a type of OCP). This equates to up to a five times increase in risk of developing MND (though the relative risk is still extremely low).

What does this mean for me?

There are many different types of pesticide. The group of pesticide that the researchers found increased the risk of developing MND are an old type of pesticide that is known to stay in the body many years after they enter it. The effects of these are well known, and have led to a ban on the use of several pesticides of this type such as DDT.

Modern pesticide use is strictly regulated and the chemicals used do not last as long in the body as the old type. The new types of pesticide could not be picked up in participants’ blood samples, and so we do not know if they present a risk factor for MND.

Dr Belinda Cupid

Dr Belinda Cupid

Commenting on the results from this study, Dr Belinda Cupid, Head of Research at the MND Association said:

“We know that people get MND due to a combination of many environmental, lifestyle and genetic factors.

“It’s unlikely that any single factor on its own will cause MND and the results in this research paper aren’t a ‘eureka’ moment. But the evidence that exposure to pesticides is a contributory risk factor towards getting MND is stacking up and I’m sure will be the focus of future research.”


What do we still need to know?

Even though this study does contribute to our knowledge on risk factors that may contribute to MND, there are still questions that need answering, such as:

  • When does exposure to pesticides need to occur to increase the risk of developing MND (such as exposure within the last X years)?
  • What level of exposure equates to an increase in risk?
  • Are all types of pesticide deemed a risk factor or is it specific ones (older versus modern pesticides)?
  • How do pesticides contribute to motor neurone damage?

More information:

Journal article: Feng-Chiao Su et al. (2016) Association of Environmental Toxins With Amyotrophic Lateral Sclerosis. JAMA Neurology. Published online May 9, 2016 doi: 10.1001/jamaneurol.2016.0594 (published open access)

Editorial in JAMA Neurology: J Cragg, M Cudkowicz, M Weisskopf. The Role of Environmental Toxins in Amyotrophic Lateral Sclerosis Risk. doi: 10.1001/jamaneurol.2016.1038

Professor Ammar Al-Chalabi wins prestigious prize

Huge congratulations to Professor Ammar Al-Chalabi for winning the prestigious Sheila Essey Award at the American Academy of Neurology (AAN) research conference taking place in Vancouver, Canada.

Professor Al-Chalabi is an MND Association funded researcher and Professor of Neurology and Complex Disease Genetics at King’s College London. He is also the Director of our MND Care and Research Centre at King’s.

The Sheila Essey Award is jointly given by the AAN and the ALS Association in the USA, and recognises an individual who has made significant research contributions in the search for the cause, prevention of, and cure for amyotrophic lateral sclerosis (ALS, a type of MND).

Prof Al-Chalabi is receiving the award for his role in helping us learn more about the complex causes of MND, including the role of genetics in the non-familial form of MND.

“It is a wonderful acknowledgement of the work the present and past members of my team have done in ALS/MND research,” Prof Al-Chalabi said. Continue reading

Janine Kirby: My 20 years in MND research

Janine Kirby is a Non-Clinical Reader in Neurogenetics and is celebrating 20 years in motor neurone disease (MND) research this month. Here she tells us more about how she got into the field, her current projects, what it’s like to work at Sheffield Institute for Translational Neuroscience (SITraN) and to meet families affected by MND.

Dr Janine Kirby

Dr Janine Kirby

How and why did you get into MND research?

Having completed my PhD at University College London, I wanted to apply my knowledge of genetics to medical research. I subsequently joined the MND Research Group at the University of Newcastle-upon-Tyne, headed by Prof Pamela Shaw, looking at the frequency of genetic changes in the SOD1 gene in MND patients from the North East of England.

Since then, firstly at Newcastle and then at the University of Sheffield, I have provided genetic input to the research strategy of investigating the molecular basis of this complex genetic disorder. I am now a Reader in Neurogenetics at SITraN working not only on the genetics of MND but also using a method termed transcriptomics (basically which genes are being switched on or off, and by how much) to discover biomarkers for the disease and to understand why the motor neurones are dying.

20 years later I’m still here because it’s incredibly challenging and interesting research, with the opportunity to work with great colleagues and collaborators across the world. Continue reading

More clues to the inner workings of the C9orf72 gene

Continuing the ‘gene hunting theme’ on from our last blog post on Project MinE, a recently published study has shed more light on the C9orf72 gene mutation.

The C9orf72 gene mutation is the most common cause of the rare inherited form of MND (about 40% of all people with inherited MND have this mutation). Some people with the sporadic form of MND also have this mutation, and it has been linked to the development of a type of dementia called frontotemporal dementia (FTD).

Figuring out the normal function of C9orf72

A study by Jacqueline O’Rourke and colleagues at Cedars-Sinai Medical Centre in Los Angeles used mice that lacked the equivalent gene to C9orf72.

When this gene was absent, the mice developed normally and their motor nerve cells were unaffected.

From this evidence they discounted one of theories about the C9orf72 mutation – that a change to the gene stops it working entirely and that this affects the health of motor neurons. Continue reading

Looking for MND genes: Project MinE update

Project MinE is an international genetics project that is analysing DNA from people with MND in detail.

For the majority of people with MND, the disease appears ‘sporadically’ for no apparent reason. For a small number of people, approximately 5-10% of those with MND there is an inherited link, in other words the disease runs in their families.

We know a lot about the genes that are damaged in the rare inherited forms of MND. We also know that very subtle genetic factors, together with environmental and lifestyle factors contribute to why the majority of people develop the disease. These subtle genetic factors are very hard to find.

The goal of Project MinE is to find the other genes that cause inherited MND and help us find out more about these subtle genetic risk factors.


Project MinE was born when Dutch entrepreneur Bernard Muller challenged his neurologist to do something with all the DNA samples in his freezer – samples being stored there for future analysis. ‘Why can’t those samples be analysed now?’ was his question. That was two years ago! Continue reading

Stem cell trials in the news

The recent announcement about the use of stem cells to treat a form of multiple sclerosis (MS), together with early results from the BrainStorm stem cell amyotrophic lateral sclerosis (ALS) clinical trial in Israel have raised the profile of stem cells as a possible treatment for motor neurone disease.

Stem cells are unspecialised cells in the body which do not yet perform a particular function. They can renew themselves and have the ability to give rise to different types of cell, including nerve cells (motor neurones and the surrounding support cells).

Both the ALS/MND study (ALS is a type of motor neurone disease) and the MS study used stem cells found in bone marrow taken from the patient, and then given back to the same patient later on in the process. The MND study gave a new use to the bone marrow stem cells, whereas in the MS study ‘corrupt/damaged’ stem cells were replaced with a new healthier set.

Below we look at both trials in more detail and describe what they mean for people living with MND. Continue reading

Respiratory support: the big debate on Symposium day 2

Different ways to support breathing were the main focus of the second clinical session on day two of the Symposium. Researchers from two MND Association funded studies presented their work looking at diaphragm pacing and also the withdrawal of ventilation support.

Lungs - Symp session pictureDiaphragm pacing

The NeuRx diaphragm pacing system (DPS) is a device developed to aid breathing by stimulating the large muscle that helps you to breathe – the diaphragm.

In 2011, the Food and Drug Agency (FDA) in the USA approved NeurRx DPS as a treatment for respiratory failure in motor neurone disease (MND). The treatment was not required to go through the series of clinical trials that is needed for a new drug. The FDA approved it on the basis of one small study because at the time the probable benefit to health outweighed the risk of using it.

Due to this lack of clinical evidence, this prompted further research in the USA and Europe to test its effectiveness on symptom management and survival. Continue reading