Ask the Expert Recap: Causes of MND
11 January 2023
11 January 2023
On 13th September 2022 we were delighted to welcome Professor Kevin Talbot from the University of Oxford to the first session of our live Ask the Expert series, answering your questions about the causes of MND. Three main areas of interest were apparent from the questions that were submitted: hereditary MND, links to sport or other physical activity, and environmental factors. Professor Talbot discussed these topics with Jill Douglas, CEO, and Sean McGrath, Medical Strategy Lead, and we have outlined some key points from the session below.
Is MND genetic?
This is a commonly asked question and to answer it, we need to understand what we mean by the term ‘genetic’. Genetic means ‘related to genes’, which are stretches of DNA that code for the proteins that our cells need to carry out everyday functions. Variation in our genes is likely to play a role in the development of MND in every case, but that does not necessarily mean that the risk of developing MND is always passed onto future generations.
For approximately 10% of people with MND, one or more other people in their family has also had the disease. In this case, the MND is referred to as ‘familial’, i.e., a change (referred to as a ‘variant’ or ‘mutation’) in a single gene determines the risk of MND that is passed on from one generation to the next. For individuals with MND because of an inherited genetic mutation, there is a 50% chance of their children carrying the genetic risk variant. However, whether carrying this variant leads to the individual developing MND is more complicated, and depends on other factors, many of which are associated with ageing.
Researchers have discovered that there are distinct biological steps (estimated number is six) that must happen before a person will develop MND. Inherited genetic mutations account for a few steps, but how many steps one mutation accounts for depends on the specific gene involved. As you can see from the diagram below, a mutation in the SOD1 gene accounts for four steps, but two more steps must happen before the person develops MND. We do not fully understand what the remaining steps are, but they are strongly related to the way the nervous system changes in ageing.
For 90% of people with MND, no one else in their family will have been affected by the disease. This is what we call ‘sporadic’ disease. In these people, genes are still important and are likely to have been one of the contributing factors to disease, but the risk variants in this situation occur in multiple genes in a complex pattern, which will not be passed on from one generation to the next. For an individual with a single first degree relative (parent, sibling or child) with MND, but no other links, the risk of developing MND is 1-2%.
Is MND related to exercise?
With several prominent sports people currently living with MND, there is a lot of speculation as to whether sport is a risk factor for developing the disease. Professor Talbot starts this conversation off by reassuring us that 50,000 people run the London Marathon every year, but they don’t all walk into an MND clinic. Taking part in strenuous exercise does not automatically put you at risk of developing MND, although he does suggest that people with MND are not a random selection of people in the population, and may have particular physical characteristics.
Obesity is less common in people with MND and they appear to suffer from few other significant health problems; they are generally slim, healthy and physically active. Scientists are still trying to understand if, in someone with the appropriate genetic background, taking part in strenuous physical activity may account for one of the steps that leads to disease. It is also possible that the genetic factors that allow someone to be good at physical activity, in some way contribute to disease in the ageing nervous system, and so the exercise itself does not cause the disease. It should be noted that a link has not yet been proven and there is ongoing research funded by My Name’5 Doddie Foundation to investigate it further.
On the topic of head injuries, there is no evidence from large populations that trauma is a significant cause of MND. Excluding the possibility that in an individual case it could be one of the steps in the pathway is more difficult, given all the complexities of the disease. The evidence of head trauma being linked to dementia is more compelling, but the type of dementia that arises from traumatic brain injury is quite different to the type of dementia seen in some people with MND.
Professor Talbot encourages people with MND to continue exercising; it carries many benefits, both physical and psychological, and does not appear to accelerate the disease process once started.
What environmental and lifestyle factors are linked to MND?
Many supporters asked about environmental and lifestyle factors playing a role in MND development. These include things like smoking, diet, vaccines, anxiety and exposure to chemicals and toxins. Professor Talbot’s view is that, based on current evidence, MND is not strongly related to environmental or lifestyle factors. For example, spouse pairs, who have shared the same environment for much of their adult lives, do not both present with the disease more commonly than is expected by chance. In addition, the incidence of MND does not vary strongly between different geographic areas, and where it does this is best explained by specific genetic factors within the population. However, he does suggest a complex interaction between genetic and environmental factors could play a role, but that large international studies would be required to investigate this.
What is clear from the session is that ageing plays a key role in the development of MND. Someone with a genetic mutation predisposing them to the disease will be healthy for decades and unaware of a problem, until the first symptoms of MND appear in their 50s or 60s. So, we can think of genetic make-up as ‘priming’ the nervous system in susceptible individuals, but ageing being essential for MND to ultimately develop. The different mixture of steps which lead to MND is likely to vary between individuals, suggesting that only when we understand individual susceptibility will we be able to apply personalised treatment.
We would like to thank Professor Talbot for his time and assistance with this series, and to our supporters for engaging and asking questions. To watch the session in full, please follow this link. If you have further questions about the causes of MND, do get in touch with us at email@example.com or on our social media channels.
Keep an eye out for information about the next session in our Ask the Expert series.