After its successful premiere in 2017, the University of Oxford organised another meeting of people affected by inherited MND, called ‘Families for the Treatment of Hereditary MND (FaTHoM)’. This turned out to be yet another excellent day where MND clinicians-researchers presented on topics such as genetics of MND, genetic testing and gene therapies. Below you can find out more about what was presented on the day and links to the videos of recorded talks.
Understanding familial MND
Introducing the rationale of the meeting, Prof Martin Turner set the scene by explaining the great difficulty in understanding the disease due to its many possible causes. Being such long cells, many things can go wrong in the motor neurones and in the vast amount of their support cells (such as astrocytes or microglia). But one factor can help us understand the disease better – genes.
Love them or loath them, the band Steps’ first single ‘5,6,7,8’ was a techno line dance song released in 1998 from their debut album ‘step one’, with the B side ‘words of wisdom’.
Using this forced and purely tenuous link and an equally awkward segue, I would like to share with you the news that the journal Neurology this week published further words of wisdom from Professor Adriano Chio, Professor Ammar Al-Chalabi and colleagues, that revisits the multistep hypothesis of MND. Their previous work showed that when no genetic cause is considered, developing MND is a six-step process. In their most recent work, the team investigated how many of the steps does a genetic mutation account for in this multistep process, with a focus on the most common MND causative genes SOD1, TARDBP, and C9ORF72.Read More »
This article was written by our Senior Clinical Fellow Prof Martin Turner, a Consultant Neurologist at John Radcliffe Hospital, Oxford.
“Will it affect my children?” This is one of the questions most commonly asked by people diagnosed with MND. The 20th century answer was a simple “no”, or at least “very unlikely”. With recent scientific advances, however, doctors must give a more complicated answer. At the same time, these advances are cause of excitement about the greater understanding of MND and new hope for treatments for all cases.Read More »
In April this year MND clinician-researchers Professors Martin Turner and Kevin Talbot at the University of Oxford organised an information day about the rare, inherited form of MND called ‘Families for the Treatment of Hereditary MND’ (FATHoM). The day was filmed and podcasts of the talks have recently become available. This article gives an overview of each talk and a link to the video.Read More »
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.Read More »
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.Read More »
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.Read More »
Mistakes in a gene known as ALS5, or spatacsin, cause a rare form of inherited MND that develops at a much earlier age than most other forms of the disease. Under supervision from Dr Cahir O’Kane, MND Association funded PhD student Alex Patto has been using fruit flies to understand how mistakes in spatacsin cause MND (our grant reference 861-792).
Prior to this research, which is based at the Department of Genetics at the University of Cambridge, nothing was known about how faulty spatacsin leads to motor neurone degeneration. Three and a half year years on, this research has shed light on this important question.
What did they find?
By conducting tests in the fruit flies, Alex has found that the spatacsin protein has a role in cell recycling (also known as autophagy), a process which keeps cells healthy. When the spatacsin protein is faulty it leads to disrupted cell recycling and abnormal levels of another protein called Rab7, which might contribute to MND development.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).
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!Read More »