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

Motor neurone signalling and the effects of RNA in MND

Dr Pietro Fratta completed his first MRC-MND Association Clinical Research Training Fellowship in 2014. Last year he was awarded a new £1.16 million Clinician Scientist Fellowship to continue his research at University College London, studying the earliest physical changes that affect motor neurons in MND (our reference 946-795). Our contribution to this four year research fellowship is £280,000.

Pietro Fratta

Dr Pietro Fratta, University College London

As his first Fellowship progressed, Dr Fratta became more interested in the field of RNA biology, where he is rapidly establishing himself as an expert. His latest project aims to see whether RNA plays a pivotal role in the earliest signs of cellular damage that occur in MND.

RNA is the cell’s copy of our genetic material known as DNA; Dr Fratta is hoping to establish if the transport of RNA molecules along the nerve fibres is impaired and if so, whether there are particular versions of RNA that are particularly important for motor neurone health and survival.

Several lab studies have shown that the process of transporting things up and down the motor neurones is impaired long before the physical signs of damage are seen. His research will seek to find out what RNA molecules are present in both the cell body of the motor neuron and the nerve fibres. Continue reading

Identifying the genetic causes of MND in specific populations

Dr Russell McLaughlin from Trinity College Dublin is one of our Junior Non-Clinical Fellows.

Our Non-Clinical Fellowships were awarded for the first time last year. They aim to retain and develop early and mid-career MND researchers conducting biomedical research. These fellowships are funded for up to four years. We are currently funding two junior and two senior fellowships.

In this three-year research fellowship, which began in January, Dr McLaughlin is studying the more subtle genetic causes of MND (our reference: 957-799).

Why is genetic research important in MND?

We know that for approximately 5-10% of people living with MND, the cause of the disease is primarily due to a mistake within the genes. We also know that very subtle genetic factors, together with environmental and lifestyle factors contribute to why the majority of people develop the disease.

It is likely that these subtle genes are quite rare, and that is why we have not found them so far. As part of his research, Dr McLaughlin is hoping to identify the rarer gene variants that may be linked to MND. Continue reading

Using iPSCs to understand why motor neurones lose their normal function in MND

Researchers can create human motor neurones exhibiting signs of MND in the lab by taking skin cells from a person living with MND and reprogramming them into motor neurones. This is called induced pluripotent stem cell (iPSC) technology and gives an ‘in a dish’ human model of MND. iPSCs are being used by several of the researchers we fund.

GBMiles

Dr Gareth Miles

Dr Gareth Miles from the University of St Andrews, together with former PhD student Anna-Claire Devlin, has previously found that these ‘in a dish’ motor neurones lose their ability to produce an electrical nerve impulse. MND-affected motor neurones at first become overactive, and then subsequently lose their ability to produce the impulses needed to make muscles contract.

In his new project Dr Miles and PhD student Amit Chouhan, alongside Prof Siddharthan Chandran (University of Edinburgh), plans to use iPSCs to investigate why these electrical properties in nerve cells change in MND (our reference: 878-792).

The researchers will look at proteins called ‘ion channels’ that regulate the flow of electrical messages (called an action potential) which travel along the nerve cell towards the muscle. Continue reading