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 →
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 →
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.
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 →
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 →
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.
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 →
In previous research Prof Kevin Talbot and colleagues at the University of Oxford began to understand more about how the C9orf72 gene defect causes human motor neurones to die. These studies were carried out using an impressive piece of lab technology, called induced pluripotent stem cell (iPSC) technology.
iPSC technology allows skin cells to be reprogrammed into stem cells, which are then directed to develop into motor neurones. Because they originated from people with MND, the newly created motor neurones will also be affected by the disease. Researchers can grow and study these cells in a dish in the laboratory. Continue reading →
Although conventional brain magnetic resonance imaging (MRI) scans are often normal in people with MND, more sophisticated MRI techniques have shown changes in the structure of their brains as the disease progresses. A limitation of even the most recent MRI techniques is that they can only provide a snapshot of the brain at a single moment in the course of the illness.
Only a description of how these MRI changes evolve over time as the disease advances will tell us how the nerve cell damage due to MND is evolving, area by area, in relation to an individual’s symptoms. This could be obtained by collecting several MRI scans from the same person over time, but the nature of MND makes it challenging to get scans showing the course of disease over several years.
We are funding a three year PhD studentship that aims to use a new imaging method to define the progression of MND (our reference: 859-792). The researcher team, involving Profs Mara Cercignani and Nigel Leigh from the University of Sussex, will use MRI scans that have already been obtained from people with MND and healthy controls. Continue reading →
Magnetic Resonance Imaging (MRI) technology is advancing rapidly as a tool for diagnosing and monitoring disease. In MND, MRI scans are used to understand changes that happen to the brain because of this disease.
Prof Nigel Leigh
Prof Nigel Leigh from the Brighton and Sussex Medical School (University of Sussex) is carrying out a study looking into changes to motor neurones using a new imaging method (our reference: 824-791).
Neurite Orientation Dispersion and Density Imaging (NODDI) is a type of MRI scan, and can see whether MND is affecting specific parts of motor neurones, called neurites, found within the brain. Neurites are the tiny parts of the nerve cells that branch out from the main body of the nerve cell, and are important in the functioning of the brain.
Prof Leigh and his team hope that the new imaging approach will tell us more about the sequence of events that cause motor neurones die, and how this relates to the symptoms of people with MND. Continue reading →
When motor neurones in the spinal cord become damaged this makes them electrically unstable, meaning they spontaneously discharge electrical impulses that cause small groups of muscles to contract. These contractions, known as fasciculations, are a common symptom of MND. Research suggests that they might be a good marker of motor neurone health.
Tracking fasciculations with surface EMG
Prof Chris Shaw
Led by researchers Prof Chris Shaw and Prof Kerry Mills, Dr James Bashford is using technology called surface EMG to collect data on the site and frequency of fasciculations in different muscles in people with MND. Fasciculations in people with MND are different to benign fasciculations, which can occur in people without the disease and are generally harmless. James and the team hope to show that fasciculations in those with MND have a unique ‘fingerprint’ which can be accurately identified and tracked.
Data collected will be compared to other information currently used to track the progression of MND. James and the team hope surface EMG might provide a more sensitive way of measuring disease progression than previously used methods. This one year feasibility study is being carried out at King’s College London at a cost of £95,000 (our reference: 932-794). Continue reading →
When diagnosing MND, it is important to look at the activity and impact of the motor neurones themselves – is the electrical message being carried down the nerve properly, and is it reaching the end of the nerve in the muscle? Malfunctions in the electrical activity at the muscle end of the nerve cell result in the muscle twitching that many people with MND experience.
One of the tests used to diagnose MND is an electromyography or EMG test. It involves putting needles into a muscle to measure electrical activity. It can be a painful and unpleasant experience, which doctors and patients are only willing to do when necessary.
There is evidence that ultrasound imaging may be able to detect the same malfunctions in the electrical activity of muscle as EMG, by looking at the way the muscle behaves when electrical activity occurs. Ultrasound images produce the typical grey scale images, for example pictures from baby scans, and can be used to provide images of any muscles in the body. Continue reading →