Motor Neurone Disease (MND), as the name suggests, is known as a disease of motor neurons, a specific type of neurons that co-ordinate our voluntary movement, leading to loss of the ability to move, speak and breathe. And perhaps because the main focus often falls on the rapidly-progressing physical symptoms and their management, the way MND affects the mind has often be overlooked.
Most literature on MND states that certain behavioural and cognitive (thinking) problems affect up to 50% people with MND, out of which 15% have a co-occurring diagnosis of frontotemporal dementia (FTD). Adding to this, a recent paper by Dr Christopher Crockford and colleagues, published in the journal Neurology, found that up to 80% of people living with MND will have some form of cognitive or behavioural impairment by the final stage of their disease (or in other words, only 20% will have an intact cognitive and behavioural processing).Read More »
In recent news, a number of press releases highlighted a paper published in the journal Cell, in which scientists, under the leadership of the University of Toronto’s Professor Peter St George-Hyslop, and in collaboration with University of Cambridge, described the process of how the FUS protein leads to the development of motor neurone disease (MND) and frontotemporal dementia (FTD).
MND and FTD – what is the connection?
We know that there is a link between MND and FTD, which in most part is caused by a mutation in the C9ORF72 gene, causing familial MND in around 35% cases and FTD in 25% of cases. Mistakes in the gene disrupt normal processes leading to toxic accumulation of TDP-43 protein in the neurons, and their subsequent death. There is however another protein toxic to neurons which results in the development of MND and FTD – the one that makes it slightly easier for us science writers to come up with witty titles: FUS (see one of our previous articles ‘What’s the FUS all about’).Read More »
In a study published in Nature Neuroscience this week, a collaboration led by Dr. Jemeen Sreedharan and colleagues from King’s College London, the Babraham Institute and the University of Cambridge have published a new mouse model of Motor Neurone Disease (MND).
The study takes advantage of cutting edge gene editing technology called CRISPR/CAS9 to generate a mouse model of the human disease that accurately mimics a genetic component found in some people affected by MND. The researchers used the gene editing technology to precisely change (mutate) the gene that the body uses to produce the protein TDP-43, a very important player in the MND story implicated in almost all cases of MND.Read More »
In light of the upcoming Biomedical Research Advisory Panel meeting happening on Friday 7 April that will discuss which new research projects the MND Association will fund, we are pleased to report on the progress of one of our already-funded researchers. In their three year project, funded by the MND Association, Prof Annalisa Pastore (King’s College London) and Prof Gian Tartaglia (University Pompeu Fabra, Barcelona) are investigating the process by which TDP-43 binds to RNA. Below is a summary of the progress they made during their first year.
Background to the project
One of the causes of amyotrophic lateral sclerosis (ALS), the most common type of motor neurone disease (MND), is related to faulty functioning of the TDP-43 protein, a component that is naturally present in all of our cells. In healthy cells, TDP-43 resides in the centre of a cell (the nucleus) where it attaches to RNA and supports correct gene expression – that is, it helps to extract information carried by a gene to form proteins, the main building blocks of our bodies.
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.Read More »
To help support people with MND who have these symptoms, and their families and carers, we need to firstly identify or confirm these signs are present and then to find ways to help manage them.
The Edinburgh Cognitive and Behavioural ALS Screen (known as ECAS) has been widely adopted as a good method of detecting symptoms of cognitive change. ECAS is a series of tests that are quick to do in the clinic and are specific to MND.Read More »
Some people with MND develop an increasingly recognised form of dementia, known as frontotemporal dementia or FTD (for more information visit http://www.ftdtalk.org/). The main symptoms of FTD include alterations in decision making, behaviour and difficulty with language.
The relationship between MND and FTD is not well understood. Prof Julie Snowden and PhD student Jennie Saxon at the Cerebral Function Unit in Salford (University of Manchester) are aiming to establish whether MND combined with FTD is subtly different to when FTD is found on its own (our grant reference: 872-792).
People diagnosed with FTD-MND, with FTD alone, and those with no form of dementia will perform a series of short cognitive tasks. These will test things including a person’s ability to recognise emotions, draw inferences about the thoughts of others, their ability to concentrate, organise actions and understand language.Read More »
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).
With motor neurone disease (MND), the muscle weakness almost always starts in a single part of the body, with the weakness then spreading to other muscles in an orderly fashion. Neurologists are usually quite good at predicting which muscles will be affected next, slightly less so at predicting when this will happen.
The physical changes on the outside will be reflecting events occurring in the ‘closed box’ that is the brain and spinal cord. The latest imaging techniques are starting to give us more of a picture of what’s happening in the central nervous system as the disease progresses, but further technological advances will still need to be made. The clearest picture still comes from the study of generously donated and incredibly valuable post-mortem tissue.
The second day of the Symposium saw researchers present in the Clinical-Pathological Correlates of Disease Progression session, focussing on how to understand disease progression, the role of prions in neurodegenerative diseases and the relationship between MND and frontotemporal dementia.Read More »
The last of our FTD awareness week blog posts is focussing on a healthcare project looking into FTD (frontotemporal dementia) and FTD-MND (FTD when combined with MND). The project began last year and is being part-funded by us.
Professor Julie Snowden and PhD student Jennie Adams at the Cerebral Function Unit in Salford (University of Manchester) are looking into the behavioural and cognitive aspects of FTD and FTD-MND.
They are aiming to work out if there are any differences in thinking or behaviour between people who have MND-FTD and those who have FTD on its own.
For example this could be looking to see if people with FTD-MND tend to show more difficulties with language, but not have many changes relating to behaviour. Or if people with ‘pure’ FTD show more difficulties with appropriate behaviour in public, compared to organisation and planning skills.Read More »