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.

Ammar

Prof Ammar Al-Chalabi, King’s College London

 

“I found out I had won by email, which I had checked on my phone while on my way to teach my medical students, so I was very excited and smiling a lot!”.

As part of the prize, Prof Al-Chalabi has been awarded $50,000 to continue his research efforts into MND.

Explaining what he planned to use the money for, Prof Al-Chalabi said: “It will help to pump prime future studies and support early stage researchers to become fully fledged investigators too, both vital steps in our fight against MND.”

Building on early accolades

This is not the first international ALS research prize awarded to Prof Al-Chalabi. In 1999 he was awarded the MND Association Charcot Young Investigator Award for his PhD research on the genetic risk factors for ALS.

Since then he has built an impressive research portfolio and published academic papers in leading science and medical journals. He frequently presents his research at international conferences on neurology and MND and is also involved in nurturing the next generation of MND researchers.

Prof Al-Chalabi’s work has covered many areas of MND research, from learning more about the types of MND and their classification, to developing an app which will alert specialist staff when someone with MND enters A&E.

Prof Al-Chalabi and his team at the Maurice Wohl Clinical Neuroscience Institute (King’s College London) have helped to identify many of the genes involved in MND development. They are now part of two large studies looking for MND genes, including Project MinE – an international project analysing the genomes of over 20,000 people. As part of this study, he is using samples from the UK MND DNA bank that the Association administer.

Away from the lab Prof Al-Chalabi is works hard to raise awareness of MND, often undertaking media interviews about his work.

For more information on Prof Al-Chalabi’s research read our ‘Research we Fund’ information sheet.

Press release on AAN website

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.

What is it like working in SITraN?

It’s fantastic. I started off with a small square of lab bench in Newcastle and now have my own office in a state of the art research institute! SITraN has allowed there to be a much better interaction between the scientists, clinicians and nursing staff, by having us all under one roof.

What are your research interests?

My research interests are the genetics of MND and how transcriptomics (measuring gene expression levels) can be used to investigate the biological pathways of why motor neurones are dying in MND and to identify diagnostic and prognostic biomarkers (‘fingerprints’ of the disease).

My research focuses on obtaining gene expression data from experimental models of the disease and from patient and control samples.

Individuals with known genetic variants linked to MND are generally indistinguishable from sporadic patients in the clinical setting, so the disease is thought to progress along common pathways which result in the death of the motor neurones. Therefore, by understanding the biological mechanisms in the genetic variants linked to the disease, it is hoped that the results will be widely applicable to other cases where the cause is currently unknown.

Can you describe the research project you are currently working on?

I am currently supervising several post-docs and students. Some of their projects involve screening our MND patient DNA samples for mutations (changes in the DNA sequence) which may cause the disease (we are currently screening TBK1). Other are analysing gene expression (which genes are switched on or off) in patient blood samples over the course of the disease or those found specifically in MND CSF (cerebro-spinal fluid) samples compared to healthy control individuals.

What do you enjoy most about your job as a researcher?

Several things really, including getting a good result, getting your paper published, getting your grant funded and seeing the students you have supervised graduate and embark on their own scientific careers.

What’s been the highlight of your career so far?

My personal highlight would be securing a permanent job as a lecturer at the University of Sheffield, which allows me to continue doing the research I enjoy, in addition to writing grants to organisations for funding new research ideas, writing up results for publication in scientific journals and supervising students.

I was also part of the team involved in setting up the MSc Translational Neuroscience course, a one year course for students who want to specialise in Neuroscience, and so train the next generation of research scientists.

What other activities are you involved with through your role at SITraN?

I really enjoy taking part in the annual open day at SITraN – last year involved extracting DNA from strawberries using everyday items including washing up liquid, plastic bags and even coffee filters! It is always great to see people’s faces when the DNA strands come out of solution at the end. I also have a Twitter account (@J9Kirby) aimed at sharing the research and my role with other members of the MND community and I have now met many followers in person.

One of the essential roles of the researcher is to also share your results with colleagues and other researchers in the field. While this usually involves publishing your data, there are also opportunities to present at European and International meetings, including the ALS/MND International Symposium. My first meeting was in Glasgow in 1997 and there were no more than a few hundred participants – there are now just under a thousand participants at the International Symposium meetings – so the research environment has certainly expanded in the last 20 years.

Who do you admire the most?

Our patients and their families for their endless support of the work we do and for participating in our research.

What do you like doing in your spare time?

I enjoy travelling, scuba diving, photography and genealogy – well, what did you expect from a geneticist! I am also a trustee of the Sheffield Hackspace, a communal workshop and skills exchange for people who make things.

 

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.

Instead they worked out that the absence of a normal C9orf72 gene causes cells in the immune system to change their shape and the jobs they do. This concurs with other theories about why motor neurons begin to die; that the cells recycling/waste disposal system is broken, and that some sort of neuroinflammatory response is involved.

Knowing more about what the gene is supposed to do in a healthy individuals will in turn help us understand how the C9orf72 mutation harms nerve cells.

More information:

C9orf72 is required for proper macrophage and microglial function in mice Jacqueline O’Rourke et al. (2016) Science 351: (6279) 1324-1329 doi: 10.1126/science.aaf1064 http://science.sciencemag.org/content/351/6279/1324.long

News story on the ALS Association website (18/03/2016)

C9orf72 research:

Read more blog posts on C9orf72  or read our ‘Research we Fund’ information sheet to see the C9orf72 projects our researchers are working on.

Inherited MND and FTD:

You can read more on our website and in our updated information sheets on inherited MND: overview of inherited MND and information on genetic testing and insurance

More information on frontotemporal dementia can be found on our blog and in care information sheet 9A

 

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.

mine

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!

How is the DNA analysed?

The technique used in this analysis is called whole genome sequencing. It is the most detailed analysis tool available to decode our DNA – and until recently was too expensive to be used in research projects. (Think of this technique as like a search engine that, rather than searching on words, is conducting its search on letters, or perhaps groups of a few letters).

Thousands of samples are being provided for Project MinE by over 16 countries around the world, including the UK. Now, thanks in part to the funds raised by the Ice Bucket Challenge around the world 4,500 DNA samples have been analysed by whole genome sequencing as part of Project MinE, from a target of 22,500 samples.

To date the MND Association has sent two batches of samples, which totals 1,400 samples at a cost of £1.4 million. These samples are from the UK MND DNA Bank that the MND Association is the custodian of, and include DNA from people with the sporadic form of MND as well as control samples.

Data issues

The art of analysing data is becoming increasingly important in MND research, creating a new field of research called ‘bioinformatics’. The researchers in this field are geneticists, statisticians and computer scientists – and their skills are being used in spotting trends, patterns and making new discoveries with genetic data, both on its own and by connecting data from different sources.

Perhaps unsurprisingly, analysing thousands of DNA samples in such fine detail generates staggering amounts of data. The data from Project MinE is being stored on a computer at the Dutch Space Centre – space research is known for generating vast amounts of data so the infrastructure is already set up. Researchers are now starting to look at how the data being ‘churned out’ by whole genome sequencing can be read and interpreted.

At the beginning of this year two new MND Association funded non-clinical research fellows began their research projects. You will be able to read more about these projects in the Spring edition of Thumb Print, out next month.

Both projects will be using data from Project MinE and other genetic research projects to tell us more about how gene variations contribute to MND. This could be working out whether it is a gene variation that causes MND in the rare, inherited form of MND or learning more about the subtle genetic contributors to all forms of MND.

More information

You can find more information on Project MinE in earlier blog posts, and on the Project MinE website. Further information on the UK part of Project MinE, the UK Whole Genome Sequencing Project, is on our website.

Dr Ashley Jones (King’s College London) holds one of our new non-clinical fellowship awards. His research is featured in our current fundraising appeal ‘See more clearly’.

More information on all of the research projects we fund is available on our website and in our newly updated information sheet.

Our application system is now open for researchers to apply for our PhD studentships grants and for our non-clinical fellowship awards. The deadline for summary applications, submitted online is Friday 29 April 2016. More information is available on our website.

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

Season of mists and mellow fruitfulness…..and prizes….

The fantastic news that Patrick Joyce and his co-inventors have won the 2015 Hackaday Prize for their ‘Eyedrivomatic’ invention is one of a number of research prizes announced this autumn.

Martin Turner award

Prof Martin Turner receiving his award from Prof Jane Dacre, RCP President

At the beginning of November Prof Martin Turner was presented with the Graham Bull Prize for Clinical Science by the Royal College of Physicians (RCP). The Prize is awarded to a member of the RCP under the age of 45 who has made a major contribution to clinical science.

The winner of the Graham Bull Prize is also invited to deliver the prestigious Goulstonian Lecture, an annual lecture given by a young RCP member that dates back to 1635 and the list of previous speakers reads as a ‘Who’s Who’ of the history of British Medicine!

Those of you who know Martin, in particular the many participants who volunteer for his BioMOx research programme will be pleased to see his new title: he was awarded the title of Professor by the University of Oxford in July this year. Aren’t Professors getting younger looking these days…! Continue reading

Heading in the right direction: Sheffield Support Snood update

We are funding, together with the NIHR i4i (National Institute for Heath Research invention for innovation) programme, a research team in Sheffield who have developed a new type of neck support for people living with neck muscle weakness as a result of a neurological condition.

Designers, clinicians and engineers from University of Sheffield, Sheffield Hallam University, Devices for Dignity, Sheffield Teaching Hospital, Barnsley Hospital, and the Sheffield MND Research Advisory Group have worked together with people living with MND to develop the Sheffield Support Snood through an iterative design process.

The results from a small pilot study of the snood were presented at the International Symposium on ALS/MND in Brussels last year, where we reported on it.

5 b (3)

Next step – the 100 collars project

In September we attended the Sheffield Support Snood training day, run by Devices for Dignity, Sheffield Teaching Hospitals NHS Foundation Trust, and Dr. Christopher McDermott, a Clinician Scientist at the Sheffield Institute for Translational Neuroscience (SITraN) who is the Chief Investigator for the project . Continue reading

Palliative Care Research – new funding available

Today an exciting announcement was made about three organisations working together to increase our knowledge on the best way to provide palliative and end of life care. The MND Association and the Chief Scientists Office in Scotland (CSO) will be working with Marie Curie on a new research call.

Marie Curie Logo

In addition to a £1million funding pot from Marie Curie, the CSO will contribute £225,000 of funding and MND Association will contribute up to £200,000. Scientists, clinicians or healthcare workers are invited to submit their outline applications by 14 January 2016.

Acting on what you told us

The areas that we’d like to fund are based on a project that was completed in January 2015, known as the ‘Palliative and End of Life Care Priority Setting Partnership’, shortened to ‘PeolcPSP’. At the core of this 18 month project were responses to an online survey, where many people shared their questions or experiences about the end of life. We were pleased that many people affected by MND took part.

From those survey responses, we worked out that there were a massive 83 topics that would be suitable for a research study (and where no conclusive studies had already been conducted). All of these are important topics to investigate, so we’re hoping that researchers with an interest in working in any of these topics will think about submitting an application for funding.Palliative-care-2

So what kind of topics are included?

The topics for the call are the list of 83 questions from this earlier palliative care research study (the PeolcPSP study mentioned above). It is too long a list to include in this post, but the overarching themes include how (best to):

  • communicate topics on palliative and end of life care
  • manage symptoms and medications
  • provide support for carers and families
  • provide support in bereavement
  • provide support for staff (and staff training)
  • co-ordinate care services
  • provide access to services
  • decide where the care should be and what type of care

Where can I find out more?

A press release and more information on how to apply for this funding is available on the Marie Curie website.

The Palliative and end of life care Priority Setting Partnership final report is available online. There’s also a video about the project explaining how it happened and why it is important.