Fathoming MND

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.

It appears that anyone could potentially develop MND. While all diseases have a genetic component, with genes influencing how the body is put together and its resistance to the wear and tear of life, relatively few diseases are determined by a single change in a gene. Such conditions are more easily passed on to the next generation and are often referred to as “hereditary” forms of the disease. The discovery in 1993 of changes in the SOD1 gene as a cause of familial MND, led neurologists to routinely ask whether any other extended family members had had MND when giving someone an MND diagnosis. Such links were clear in the family history of at least 5%, though this was probably an underestimate as there are many reasons why people might not know about their family in sufficient detail. Where a family history of MND was clear however, a longer discussion took place around the option of trying to identify the gene affected. Twenty years ago, such genetic testing in those with a family history of MND had only a 20% chance of finding a positive result, and a lot of uncertainty.

Then in 2011 it was discovered that a previously undetectable change in the gene C9orf72 was not only the commonest cause of hereditary MND (nearly twice as common as SOD1), but also the commonest genetic cause of a related condition: frontotemporal dementia (FTD). Moreover, the two conditions were found to independently affect members of the same family. This now meant needing to extend the family history discussion to include asking about relatives with dementia. When blood samples donated for research by a large group of people living with MND regardless of any family history were screened for the C9orf72 mutation, the test was positive in nearly 10%.

Knowing the cause is important for many people living with a condition like MND, one that often appears to arise suddenly on a background of apparent physical fitness. The discovery that it is a genetic change then brings up the challenge of how best to share the information with siblings and children, who are at 50% risk of being carriers of the same genetic change. Being a carrier does not guarantee developing MND or FTD in one’s lifetime but knowing that this risk is greatly increased can be deeply unsettling. Equally, knowledge can be empowering for some relatives who may wish to use the information to guide their own family planning.

A further development is early promise seen in other neurodegenerative conditions by applying treatments that target genetic changes e.g. babies with spinal muscular atrophy. Similar types of treatment are now being tried in people living with MND caused by SOD1 gene changes, and similar therapies aimed at the much more common C9orf72 gene change are expected in the near future. It is not certain that such treatments will work, and at present they would only be suitable to try in those whose MND has an identifiable genetic code error as the cause. However, even the possibility of therapy trials for at least 10% of all MND means that offering testing to all newly diagnosed cases of MND (and FTD) is starting to become more routine. Genetic testing always requires detailed discussion with doctors familiar with the issues, so that individuals can weigh up the benefits versus any concerns in an informed way before making a decision about being tested.

With such rapid and complex developments and the need for wider education, Families for the Treatment of Hereditary MND (FaTHoM) was conceived. The aim is to create a forum for the issues facing all of those affected by hereditary forms of MND. They include genetic testing and emerging therapeutic trials, but also vital non-therapeutic research such as disease activity (bio)marker development, which will be needed to measure the effectiveness of any future preventative therapies. The MND Association sponsored the first event held Oxford in 2017, which involved a series of talks that can be viewed here.

The insights gained from research on hereditary forms of MND have value for the wider aim of developing treatments for the great majority MND cases, even though they are not hereditary to the same extent. Understanding hereditary MND helps us understand how MND develops more generally, and therefore what types of treatments might work best. I hope to encourage further events around the UK, and to engage many more families affected by hereditary MND in education and research.

2013 martin turner image

Prof Martin R. Turner 
Consultant Neurologist
Medical Research Council & MND Association Lady Edith Wolfson Senior Clinical Fellow
Oxford MND Care Centre Co-Director
John Radcliffe Hospital, Oxford


Find out more about inherited MND in our research information sheets:

Networking to progress in the world of science: Mini-Symposium on MND

Conferences and symposia are a crucial part of the research world – not only for the amount of knowledge that is communicated to large audiences but also for the exchange of ideas on a more inter-personal level. Novel ideas are created there as well establishment of collaborations that might lead to new research projects and clinical trials – all in all, putting a bunch of researchers in a venue with a projector, coffee and biscuits can only lead to good things!

One of the recent events that I had the pleasure to attend was a small-scale conference – the Mini-Symposium on generic disease mechanisms in MND and other neurodegenerative disorders. Held at the Brighton and Sussex Medical School in late June, this event was a precursor to the inauguration of a new MND Care and Research Centre for Sussex, directed by Prof Nigel Leigh. Continue reading

More information for families affected by inherited MND available online

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. Continue reading

AMBRoSIA – our biggest ever research project

The AMBRoSIA (A Multicentre Biomarker Resource Strategy In ALS) project is our biggest, most ambitious research undertaking to date. The project funding began in August, closely followed by being the focus of this month’s ‘Make Your Mark’ fundraising appeal. Here we explain more about what this flagship project is all about. Continue reading

Developing the Biomarkers in Oxford Project

Biomarkers in Oxford (BioMOx) is a research project with the aim of identifying a diagnostic biomarker for MND, which could be used to track the progression of this condition.

What are biomarkers?

The aim is to identify biomarkers, or ‘biological fingerprints’ for MND. This could be through testing blood and spinal fluid (CSF) samples from people with MND, or using MRI scans and other imaging techniques to look at changes in the brain.

By understanding the very earliest changes detected in these samples at the start of MND (the biomarker), it is hoped that they could be used to work towards disease prevention and to develop more targeted therapy for those already affected by MND.

For example, including a biomarker element in future clinical trials will help us learn more about the disease and identify participants most likely to benefit from the drug being tested.

Being able to track the progression of the disease could also help with effective care-planning for people with MND. 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

On the seventh day of Christmas MND research gave to me: Seven research strategy themes

“On the seventh day of Christmas MND research gives to you… our SEVEN research strategy themes”

It’s New Year’s eve, a time to look back and celebrate on 2014 and our MND research achievements. It’s also a time to look to the future; in 2015 we will be funding new MND research in line with our research strategy.

Our 2010-2015 research strategy focuses on seven key themes.

causes1) Identifying the causes of MND

The exact cause of the majority of cases of MND is still unknown. Therefore identifying the causes is our first step in understanding MND and developing future treatments.

In 2014 we identified two new inherited MND genes and also announced funding for the UK Whole Genome Sequencing project to better identify the rarer genetic factors involved in causing the disease. Read more.

models2) Create and validate new models

Once we identify a genetic cause of MND, we need to find out how this gene causes MND. Animal and cellular models help us to find out how the gene affects the motor neurones and how this causes disease in a complex animal system. Continue reading

Neurofilaments show promise as biomarker candidates for MND

TiskSaturday afternoon saw the 25th International Symposium on ALS/MND expand from two to three sessions running in parallel. Times have changed from the early years of the meeting when sessions finished at lunchtime on the second day because there wasn’t enough stuff to talk about! Rather than flitting between three different lecture halls, I opted to immerse myself in the Biomarkers session, especially since the session was being kicked off with presentations from MND Association funded investigators.  Continue reading

Developments in BioMOx

Medical Research Council (MRC)/ MND Association Lady Edith Wolfson Senior Clinical Research fellow, Dr Martin Turner writes about recent developments in his BioMox study.

Dr Martin Turner, MRC/MND Association Lady Edith Wolfson Clinical Research Fellow

Dr Martin Turner, MRC/MND Association Lady Edith Wolfson Clinical Research Fellow

My first ever blog. I decided to share developments in ‘BioMOx’ – the Oxford Study for Biomarkers in MND, which has been funded through the MND Association’s pioneering Lady Edith Wolfson Fellowship scheme (in conjunction with the Medical Research Council).

About BioMOx

Between 2009 and 2013, over 70 people living with MND (and some healthy people of similar age for comparison), took part in a new type of patient-based study. Men and women of all ages (from 28 to 86), some with primary lateral sclerosis (PLS) as well as a range of the more common amyotrophic lateral sclerosis (ALS) types, all gave up their time to attend for a day or two of tests in Oxford. Continue reading

Taking part in BioMOx..

To end volunteer week, Katy Styles, who is a Campaigns contact for the East Kent Development Group of the MND Association, blogs about her and her husband Mark’s experience of volunteering to take part in the Biomarker’s in Oxford (BioMOx) study.

It started as an innocuous question following a neurology appointment at the Oxford MND Care Centre, Mark and I asked “Now what can we do for you?”

Following a phone call and some form filling, Mark and I had volunteered to take part in Dr Martin Turner’s BioMOx Project. Mark as a person with MND and me as a control of the same age.

We didn’t know what to expect as we were scheduled to take part in two days worth of tests, which included two scans and a written test. In between time in the scanners however, we were able to enjoy everything Oxford has on offer. Continue reading