Motor Neurone Disease research has long been underfunded, but the pathway towards better treatments – and potentially a cure – seems within reach.
Over 2000 people are diagnosed with motor neurone disease (MND) in the UK each year. In the US, this figure is closer to 10,000. Of these people, a third die within the first year of diagnosis.
The condition is historically underfunded with only one approved drug in the UK – Riluzole – which has been prescribed for over 20 years. The medication is said to extend a patient’s life by around three months, but there is no cure or treatment that can reduce the rapid deterioration associated with the disease.
Over the last ten years, MND has begun to receive greater interest from the general public, particularly in the UK where several high-profile sports personalities have been diagnosed and spoken publicly about their experiences with the debilitating disease.
The ice-bucket challenge which swept across social media in 2014, raised masses of awareness and injected substantial funding into MND and neurological disease research and care. The impact of this funding now appears to be coming to fruition as promising new studies point to possible pathways to a cure and more effective treatments. Pharmaceutical companies are also catching wind as they begin to see new opportunities in MND.
Now, thanks to this boost in awareness, larger funding pots and a growing international workforce, many experts believe a cure is within reach.
“MND isn’t incurable, it is underfunded,” Dr Nick Cole, head of research at the Motor Neurone Disease Association, told NR Times. “There is an answer out there; something causes MND. It will be found, it just requires the funding and the brains to do it.
“It feels like now the rate of discovery is accelerating. The number of papers that are published every year is increasing [and] we’re getting into the real granularity of genetics.”
Breakthroughs in biomarker research
One of the reasons MND is so difficult to treat is due to the rapid progression of the condition. When a person is diagnosed they are likely to have already lost 40 percent of their neurons before beginning a course of therapy.
“The analogy here is that the house has almost burned down by the time you begin to try to put the fire out, which makes it very difficult to turn around [because] of the damage that’s already done,” Dr Cole said.
For many years, scientists have been searching for biomarkers that can allow neurologists to detect MND before symptoms present themselves. After decades of research, there are now several potential biomarkers that are coming to light which could prove effective.
One such biomarker is neurofilament, which Dr Cole describes as the “scaffolding that holds neurons together as they degenerate”. Neurofilament breaks off into the bloodstream and spinal fluid which can then be measured to give a readout of neuron loss.
A new genetic therapy, known as Tofersen, also might be a game changer for some. The reason that it is important is because of its ability to fight against a gene associated with MND called SOD1.
“When a protein is made from the DNA of a ‘faulty’ gene, a photocopy is made of that particular gene and that’s made into a protein,” Dr Cole explained. “The way this therapy works is [Tofersen] attaches to that photocopy and effectively destroys it.”
Clinical trials have found that levels of neurofilament and the SOD1 protein were reduced after the administration of Tofersen. While participants’ ALSFRS (functional rating scale for people with MND) did not change at first, improvements were observed over longer timeframes.
These results suggest that Tofersen could potentially be an effective therapy, but only for a small proportion of people as just one percent of MND patients have a SOD1 mutation.
“It’s a proof of principle, it’s the first cab off the rank for this kind of gene therapy treatment,” Cole added. “There are several now that are in development for other genes, some of which are hoped to work for everybody with MND, which would be absolutely incredible. We might actually be very close now to a potential therapy.
“In terms of a timeline, there’s a trial still ongoing and they are going to submit the data to the relevant authorities to see whether it could potentially get approval and what will be needed for that.”
The road to a cure
A pre-symptomatic trial is underway exploring the potential of using neurofilament as a warning signal for MND. The study involves a cohort of people who do not show symptoms but are known to have the SOD1 mutation.
“In those people, they are monitoring the level of neurofilament in the blood,” Dr Cole explained. “Before symptoms, you see a rise in neurofilament levels, so as soon as that neurofilament level rises to a certain point, they start being given the medicine in the trial.
“The idea is that those people will never develop the MND symptoms because the faulty SOD1 protein will never be made and they won’t lose so many neurons before they start to develop MND symptoms. That’s pretty mind-blowing and for those people it would potentially be very effective; a cure effectively.”
This is just one of many pathways to a cure that is being studied by scientists across the world. Other genes that are known to be associated with MND are being studied to search for causes of the condition. For example, a fault in the gene C9orf72, which is the most prevalent genetic cause of MND, is being researched around the world to try and prevent the faulty gene from being produced.
Other research is exploring the role of specialised cell types which are instrumental in maintaining the health of neurons. One of these cells, known as microglia, prevent infection and keep harmful invaders at bay. However, an overactive immune response – which is associated with MND – might lead to these cells attacking the body’s own motor neurons. Scientists are now beginning to understand more about how these cell types work and what role they play in MND.
The growing role of technology
Recent accelerations in the research space can be partially attributed to improved standards of technology in the genetics of biology and the genetics of MND.
“With ever-increasingly powerful computers and more rapid sequencing of genomes, there’s more understanding of some genetic components of MND, and genetic components of biology as well,” Dr Cole said. “[This] is really important for understanding how to develop new therapies.”
Technology is also playing an increasingly vital role in care. Three years ago, the MND Association launched the MND Association NextGen Think Tank which was co-founded by Rolls Royce and brought together some of the biggest players in the tech world, including Google, Microsoft, Dell, Intel, Vodaphone, BT and Rolls Royce.
Given that approximately 80 per cent of MND patients experience speech loss, the group put a particular emphasis on the development of technology that can improve patients’ ability to communicate.
The MND Association has since collaborated with tech firms on various projects, the most well-known being ‘I Will Always Be Me’. The project – led by Intel, Dell and Rolls Royce – aimed to improve the process of voice banking for communication devices. This previously involved sitting alone in a room reading and repeating monotonous phrases. But now, thanks to the work of the MND Association and its partners, patients can complete the voice banking process by reading a short, illustrated book authored by New York Times bestseller, Jill Twiss.
The e-book – designed to be a shared experience for family and friends – is written from the perspective of someone living with MND explaining to their loved ones about the condition and their experience with the disease.
Other projects include an initiative with Google to train Google assistants to understand slurred speech and a collaboration with Toyota to bring support robots into people’s homes.
“It’s the first time I’ve ever seen people coming together; competitors and big tech companies,” said Nick Goldup, director of care improvement at the MND Association. “We have companies in the same room such as BT and Vodafone. We had the last summit at BT’s head office and we were talking to all these companies about how we can access various different technologies they have; it’s amazing.”
Updating the NICE guidelines
The first NICE Guidelines for MND were published in 2016. Since then, more patients have been getting access to multidisciplinary care which brings together a group of healthcare professionals from different fields. For a complex condition such as MND, this may be contributing to people living longer.
“There have been some studies that suggest if you get access to multidisciplinary care, it will lengthen your life,” Goldup said. “Only by a small amount but by having access to that sort of care and support does make you able to live longer with MND.”
Seven years on, the MND Association is now reviewing the existing NICE guidelines to account for recent advancements across research and care. The organisation is currently building an evidence base around these gaps which include access to voice banking, the impact of exercise on MND and the need for better psychological support to name three.
“The care that’s available throughout the NHS for people with MND is amazing and there’s teams of wonderful people that are looking after the community,” Goldup said. “But, there are some aspects of care that have varying degrees of access in certain areas, like psychological support. That’s always been a bit of a gap, I think we need to see what we can do to help people get psychological support for them and their families.”
A fundraiser for the Motor Neurone Disease Association.
£50 million government funding
Boris Johnson announced in November 2021 that the UK Government would ringfence £50 million for new MND research over the next 5 years. Researchers were initially told they would need to make between 100 and 300 applications to access the funds. After lengthy talks between the United to End MND coalition and the Department of Health and Social Care, a compromise was met in June of last year that would see the researchers submit around three or four applications a year for funding.
Six months later, the government announced that £29.5 million of the allocated £50 million would be invested “immediately” through specialist research centres and partnerships with leading researchers.
Talks are still underway to determine how the remaining £20.5 million will be distributed with the United to End MND coalition continuing to highlight its desire to avoid funding via multiple disjointed pots of money.
“The concept is to create a virtual Institute where all of the researchers will work together,” Dr Cole added. “Instead of everyone having to apply for individual little grants it would be one big coordinating push.
“In terms of what will happen with it, hopefully it will be a springboard to other funding as well, because it’ll allow this coordinated approach. It feels like we’re so close that it may just be the thing that we need.”
