Fathoming MND

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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:

The MND Association’s vision is a world free from MND. Realising this vision means investing more in research, further developing partnerships with the research community, funding bodies and industry, while ensuring that advances in understanding and treating MND are communicated as quickly and effectively as possible. Our Research Development team, composed of 11 members, work hard to achieve this. Principally, the Research Information team within this are involved in communication activities including this MND Research blog.

1 thought on “Fathoming MND

  1. Good article. A good point to note about the current gene therapy testing for SOD1 is that we don’t even know why/how defects/mutations in SOD1 are disease causing (although I stand to be corrected on this matter). We are going to have to be very careful in how we progress, and we could be looking at a scenario where a treatment may be denied to the wider community. Now that is quite right when there is 100% proof of zero effectiveness shown in the wider community. But in the place we are at with MND, in stark contrast to Cancer, we have only 1 drug. Just look at the history of Riluzole and the trouble that specifying for “ALS only” might have caused in denying access to the drug for pls, Pbp, Pma, and in “indefinite MND”. So for example imagine the SOD1 gene therapy trial is successful. Do we then carry out a separate trial or do we just get the potential solution out in the wild?

    It will be a reasonable debate to start now.

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