Big Walk stories: supporting neurological disease research at Sheffield

• Dementia affects over 830,000 people in the UK, and approximately 36 million people worldwide.
• Stroke is one of the leading causes of death and long-term disability, affecting over 120,000 people in the UK every year.
• Each day, 80 people in the UK are newly diagnosed with Parkinson's disease, which affects over six million people globally.
• Multiple sclerosis (MS) is the most common cause of disability in young adults, affecting over 100,000 in the UK
• MND kills six people in the UK every day, with a third of those diagnosed losing their lives within just a year.

Andrew Myers - alumnus and Parkinson's patient

BA Hons Philosophy 1985, MA Applied Social Studies 1991, PG Cert Creative Writing 2014

I was diagnosed with Parkinson’s disease at 53, which is relatively young. It can of course happen much earlier, which is especially tragic. It generally happens a little later in life than 53 though, so it was definitely a real blow for me.

It started with a strange awkwardness in my left arm. At first it just wasn’t swinging naturally, and sometimes if I was making a cup of tea with my right hand, the left arm would sort of creep up across my chest.

It saw it affecting my guitar-playing, and later my driving. We were coming home from a lovely holiday in the early hours one morning, and my arm felt like lead, to the extent I thought I might have trouble changing gears. I’d known something was up, of course, but I was really taking it seriously by then.

Even so, the diagnosis absolutely knocked me for six. I went straight from the hospital into Weston Park, which I’ve known all my life - I played there as a kid - and just walked around a bit to get some fresh air. I phoned my partner at work, and we had a very basic sort of conversation, but I said I didn’t know too much about it at that point; there was a lot of ‘finding out’ to do.

I think I was a bit shocked and stunned really, and it took a while to sink in. Then I started reading about it, and that’s when it began to feel more real.

A life-changing diagnosis

The fact that Parkinson’s isn’t fatal in itself was made emphatically clear to me right at the start, before I got too depressed about it. But it can certainly give you a good kicking. In some ways it’s a hidden disability, but I wouldn’t underestimate it in anybody.

It has a profound impact at any stage, and certainly has had on me. My life has changed a lot since.

For one thing, it meant I had to retire about 10 years prematurely, which had a financial impact on the family. In some respects I felt relieved to finish work early, but I lost access to a lot of amazing people and stories. It really did affect my sense of self - without that structure and purpose in place, I found myself somewhat at sea. I still am.

We got our dog Chester after I was diagnosed. I was a little cagey about it, but I really fell in love with him and he kept me going, getting me out and about. I used to go long-distance hillwalking though, and I’d always hoped to spend a lot more time in the hills, maybe explore Scotland. I don't feel I can really do that now.

When I’m especially weakened, there’s a sort of free-floating anxiety that wafts in. I’ll overplan all the time as a way of coping, which does take the fun out of things to some extent. I suppose everyone’s different, but I’ve always been fairly robust, so that’s been another big change for me.

The work SITraN is doing today is profoundly exciting. For people in future, rocking along quite nicely when all of a sudden their world is blown apart by a diagnosis like mine, it will make a world of difference."

Trialling treatments, meeting challenges

For the first few years, my treatment seemed quite straightforward. The doctors would just chase the symptoms with medication. I’d lose movement due to a lack of dopamine in my brain, take different combined drugs to counteract it, and the movement would come back. But it’s stopped being like that now really.

Parkinson’s slows me down, diminishes my speech, immobilises me…it really cramps my style! But these drugs are powerful substances, so it’s always a matter of titration. They have to try me with varying doses and see what works; too much of the dopamine-type ones can overdrive me. I get a bit jerky and talk more rapidly, and that’s not good either. It doesn’t feel like me.

I often feel as though huge swathes of my life now are spent just waiting for my movement to come back. I'm exhausted when I'm feeling 'off', and can only do a modest amount. I think the biggest thing is that feeling of a loss of time, like I'm falling behind in my life. There’s just never enough time.

New innovations, new hope for the future

I've been experiencing more of those difficult side effects of late, so it’s always about trying to get the medication right. That's why the personalised treatments being pioneered in Sheffield are an amazing concept to me. Truly a wonderful thing - almost sci-fi!

When I met with Professor Oliver Bandmann at SITraN, he explained to me how medicine in the future will be specifically tailored towards individuals. It just sounds astounding really, almost miraculous in fact. Because again, it really boils down to time.

If you're in a position to support SITraN, and feel inclined to give to the future of neurological research, I think theirs is a profoundly exciting project. 

Without being too overly altruistic about it, the work being done today may not benefit me directly. But for later generations - people younger than me and rocking along quite nicely, when all of a sudden their world is blown apart by a diagnosis like mine? For them it will make a world of difference.

Dr Ali Ali - stroke researcher and clinician

Senior Clinical Lecturer, Cerebrovascular Disease
Honorary Consultant Geriatrician and Stroke Physician

Stroke is a major problem because it's so prevalent. Around 15 million people globally will suffer stroke each year, with about 120,000 of those in the UK. In Sheffield alone there are probably 3,000-4,000 people living with severe impairments after stroke, meaning they're unable to return to work or leisure activities.

One of the key things about stroke is that it's so sudden, people just aren't prepared for the consequences. Survivors often need mobility aids, and assistance with some or all of their daily activities. It’s sometimes thought of as a ‘later years’ condition, but a quarter of the patients we see are of working age, with young families or other dependents.

As a clinical academic, around 50% of my time is spent with patients in hospitals, and the rest is research. Initial therapies aim to limit the amount of damage the patient experiences. Later in the patient’s journey, we focus on facilitating and encouraging as much rehabilitation as possible.

Exploring physical and emotional recovery at SITraN

About half of all stroke patients will experience difficult and frustrating mobility challenges. That can mean struggling to walk or hold things, let alone more complex tasks like writing or bathing. This creates major physical and psychological obstacles, sometimes exacerbated by difficulty with speech and language.

Coming to terms with suddenly being unable to walk or speak is incredibly tough, and there's often a real grieving process early on.

Anxiety, depression, and extreme fatigue often hold patients back from fully engaging with a rehabilitation strategy. Any of those would be a serious issue on its own, but in reality most patients will experience some combination of all of them. It’s not hard to see why so many people struggle to regulate their emotions following a stroke.

At SITraN, we’ve recently been working on a multi-phase trial for a procedure called TRICEPS, using in-ear electrical stimulators to trigger brain signals during recovery exercises. The goal is to help rebuild damaged pathways faster, and we’ve already had people reporting quite profound progress in arm functions after a 12-week trial at home.

I’m now hoping to do something similar with a home-based speech and language programme, an area that doesn't always receive enough targeted support. We’re also about to open up a study into a fatigue-alleviating treatment called ischemic conditioning, aiming to bring in a wider group of patients across Sheffield, Doncaster, Rotherham and Barnsley.

Patient and public involvement is central to our work these days; it ensures our output directly benefits the people we’re here to help. So much in research relies on donor funding - without the generous backing of our alumni and supporters, a lot of the studies, new therapies and discoveries we’re making just wouldn’t happen."

Sheffield's unique strengths drive innovation

We're lucky in Sheffield to have a deeply embedded group of individuals working on stroke research. We've got multiple consultants developing studies and recruiting patients. Close links with Sheffield Teaching Hospitals mean we have lots of different clinicians connected to lots of different patient groups.

They really understand the problems people are facing, because they're tackling them on a daily basis.

Another key SITraN strength is the pull-through of preclinical work into clinical work. People like geneticists and metabolic experts all bring new ideas and skills to lab-based projects, so we can feed that into patient testing in a highly organised way. The translation process from bench to bedside feels really robust.

We also have a foundation of strong undergraduate and postgraduate researchers, which is extremely important.

Delivering a range of courses like clinical neurology, translational neurology and neuropathology takes a lot of effort and investment, but it means access to really interested, motivated graduates. We always want to bring them through into postgraduate studies and jobs, so the donor community's generosity towards research funding at Sheffield is incredibly valuable.

Your help changes lives

Patient and public involvement is hugely important to our work these days, and that helps ensure our output directly benefits the people we’re here to help.

In research, so depends on securing additional funding: without the kind backing of Sheffield alumni and supporters, a lot of the studies, new therapies and discoveries we’re making just wouldn’t happen. Campaigns like the Big Walk help us explore whole new avenues of neuroscience, and create genuinely life-changing therapies.

When you see first-hand the impact our work can have on such large numbers of people, both now and in the future, it really drives home how vital this work is. Thank you so much to everyone who supports us - you really are doing something incredible.

Sean Davies - MND patient and tofersen recipient

NIHR Sheffield Clinical Research Facility

I’m a father of five children, and a husband who’s been married to my wife now for 30 years. I’m an employee of local government, and a productive member of the community. I'm also a runner - I've always enjoyed running, it’s a wonderful thing to do. It gets me out and helps clear my head.

My father died of MND; I watched him pass away. My grandfather we believe died of it, I have an aunt who died of it, I have uncles who died of it. It runs in my family, and it’s been slowly progressing in myself.

I’d noticed the impact of my illness on my mobility more as my times got worse and worse, but in the past year I’ve been having the tofersen injections.

What this treatment represents, in real terms, is genuine hope. Hope is not something to be underestimated. The difference it makes is simply enormous.”

The impact of pioneering treatments

What difference does it make?

Well, if you know the Hallamshire hospital in Sheffield, you’ll know there are a lot of stairs in there. I get my injections on floor M, so it’s quite a way up. I can now get up there in less than three minutes, which is faster than the lift!

So if anyone else ends up visiting there and feels like a challenge, try those stairs out for yourself - and bear in mind that, thanks to Tofersen, someone with MND can currently make it up there in around two minutes and 55 seconds.

What difference does it make to my family?

As I said, I have five children. We know what the future holds; we know there’s a 50% chance that each one of them might have MND. The fact that this system is working means we have some hope.

Rewriting a future with hope

MND didn’t used to be like other diseases. For most conditions, even when the prognosis is challenging, there’s usually hope.

But I know what happened with my father, and how the landscape was when I was first diagnosed with MND - there was no hope, there was no treatment. There’s nothing: you already know how it’s going to end, and it’s not a nice end.

What this treatment represents, in real terms, is genuine hope. Hope that I will be around here longer as a father, as a husband. Hope that I can still go out there and do my job in the future, and continue to be a productive member of society.

Hope is not something to be underestimated. The difference it makes is simply enormous.

Tobias Moll - MND research fellow

MND Association Lady Edith Wolfson Fellow

My research has focused on MND since I started my PhD here at SITraN back in 2017. I've since finished that and done two separate post-doctoral roles, specialising in characterising novel genetic variants of MND.

My team uses complex machine learning to identify new disease-causing gene mutations, and I model them in patient-derived motor neurons to study their effects. We can then identify new disease mechanisms, and potential new ways to target them with drug treatments.

The drugs we're looking at may already be on the market, or it might lead us into a whole new area of disease biology we’d never considered before.

Last year I got my first fellowship awarded from the MND Association to study activity in the ‘lipid rafts’, or the membranes around the edge of neurons. Although quite heavily researched in cancer biology, it’s an exploratory area for MND that's starting to gain a lot of traction.

World-leading breakthroughs and discoveries in Sheffield

The findings we come across can be really exciting. We recently identified a mutation that was increasing levels of a particular protein, affecting the neuron’s primary cilium (a sort of signalling antenna). This was effectively a new area of biology, because hardly anyone was researching that in neurodegenerative disease.

We then used a drug - the same type used in the tofersen SOD-1 trial here in Sheffield - to silence the gene responsible. We've since been able to rescue disease phenotypes in mouse cells, and see an almost complete recovery. That’s a phenomenal result: the neuron lifespan was tripled, which is incredible for a disease as aggressive as MND.

We're now teaming up with companies to have a therapeutic-grade drug synthesised, which we’re hoping to get to clinical trials soon. Based on the evidence so far, I’d hope we've got a lot to be excited about.

With the sorts of breakthroughs we’ve been making, the past couple of years have felt like a bit of a watershed...the quality of the work being done at Sheffield is right up there with the very best anywhere in the world."

Because MND is so aggressive, what patients rarely have enough of is time. One recent initiative aimed at trying to speed things up is Experts-ALS, co-led by SITraN's Professor Chris McDermott. It brings 11 different UK MND centres together to screen experimental drugs for ALS, the most common form of MND, and should mean we can spot any potential human benefits faster than ever before.

A dynamic, multidisciplinary approach

At conferences all over the world, I see just how pioneering SITraN is - the quality of the work being done at Sheffield is right up there with the very best. With the sorts of breakthroughs we’ve been making, the past couple of years have felt like a bit of a watershed, and clinical trials are starting to come thick and fast.

I think the fact that we’re very multidisciplinary is key. We don’t rely only on scientists to make these discoveries, but clinical and technical workers, doctors, nurses, patients, caregivers, engineers. Without bioinformatics, I've got no gene mutations to model in my cells, and without clinicians, bioinformatics have no patient DNA samples to work from.

SITraN is designed from the ground up to align with that concept, and the workflow benefits are enormous.

Supporters are forging the future

I was recently at the University’s Forged in Sheffield, Shaping the Future campaign launch event at the Royal Institute in London, and I was talking to representatives of the Ian Pratt MND Foundation. Ian was someone who lived with MND and who also did a lot of fundraising for SITraN. His relatives and supporters were all incredibly grateful and supportive of what we’re doing.

Every time that happens, it really reignits my energy around wanting to drive the research further and faster.

My PhD was donor-supported by someone living with MND, and my first postdoc was provided by a generous backer who also has a personal connection to our work. So in a very real sense, I’m here today thanks to the kindness of the University’s supporter community, and it’s such a powerful motivation to keep pushing forward.

Dr Daniel Blackburn - dementia and Alzheimer's research

Senior Lecturer, Neuroscience
Honorary Consultant Neurologist

I diagnose people with dementia every week, and the truth is it’s a horrible disease. People can live well with it, but generally only if it’s diagnosed early. If it goes unrecognised for too long, it usually means that neither the patient nor their families can get reliable access to treatment.

I'm currently working on non-invasive scalable techniques that diagnose dementia, and the diseases that cause it, at an earlier stage.

I’m predominantly doing that using a web-based speech app, called CognoSpeak, that I co-led on the development of. (It actually has three variants; CognoSpeak, CognoMND, and CognoStroke, each targeting different specific areas of neurological research.)

By using AI and speech technology to analyse language patterns, CognoSpeak can identify potential early signs of dementia and Alzheimer’s disease faster and more efficiently. Research has shown it to be as accurate in identifying and predicting Alzheimer's as more traditional methods, and much quicker too.

Meeting current challenges head-on

There’s a real clinical need for this kind of technology-led approach at present. We don’t have enough clinicians in the UK to stratify and diagnose people, and GPs don’t have the time, skills or tools to do it as part of primary care. There are long waiting lists for memory clinics all over the country.

As a web-based tool, CognoSpeak can help address serious inequalities in access to those types of services, making early diagnosis available more widely. Being able to engage remotely makes it better for rural communities, or people who might otherwise struggle to attend an in-person appointment.

It also helps populations that are under-served and underrepresented in clinical settings. We worked with groups like South Asian, Chinese and Somali communities in its development, ensuring that specific accents or pronunciations wouldn’t introduce any unhelpful bias.

As a clinician working to diagnose people, you do feel the impact of that renewed hope. Being able to tell my patients we’ve got active research ongoing, and that there are new treatments coming along, is crucial."

Most of my research is in diagnosis, but in treatment terms I lead phase 1 studies. Sheffield is one of only three UK sites that can do them for dementia, so a challenge we're currently looking to address is around engaging more people in early stage research here at SITraN.

It’s still relatively rare for people with dementia to take part in any sort of dedicated research, whereas it's much more common for many other diseases. Without more people taking part, we won’t get new treatments.  It’s really important that we’re able to reach more people across South Yorkshire going forward, giving the whole region an opportunity to be involved.

Tomorrow's solutions today

A key strength of SITraN is the fact that we’ve got clinicians, bioinformaticians, various neurological specialties and scientists all working alongside each other. We’ve effectively got everything under one roof, from the cell model base all the way through to phased clinical trials.

Being just across the road from the hospital, those important links are really well-established too. Other sites are often far removed from working hospital settings, and therefore from patients. 

An especially exciting development we’re pushing against at the moment is around the standard approach to Alzheimer’s treatment. For years now, drug interventions have targeted amyloid proteins, but with limited effect. We’re now getting much closer to targeting other areas at SITraN, focusing on the metabolic deficits we see in the brains of people with Alzheimer's, and developing new treatments for those.

As a clinician working to diagnose people, you do feel the impact of that renewed hope. Being able to tell my patients we’ve got active research ongoing, and that there are new treatments coming along, is crucial.

In future, I believe we’ll be able to stabilise the progression of the disease. If we can do it here, the benefit for millions of people - and society as a whole - will be enormous.

Dominic Shadbolt - alumnus, MS patient and advocate

MSc Politics with Research Methods 2017

For over 30 years, I’ve been living with multiple sclerosis (MS), a journey that began at 23 when I noticed something wasn’t quite right while out running. It started with a strong buzzing sensation down my arms and legs as I tipped my head forwards - a sensation later identified as Lhermitte’s sign, caused by a lesion in my neck.

At the time, MS was a diagnosis without effective treatments, presenting a challenging path forward. In those early years, I approached my condition with a determined mindset, attempting to push through; a very 'young man' response in hindsight.

I soon learned that with MS, there are no straightforward trajectories. The unpredictability of the condition taught me resilience and adaptability, prompting me to think creatively about how to manage my life and maintain my passions, like cycling.

An evolution in treatment at Sheffield

I’ve since witnessed a remarkable evolution in MS treatments, from the first attempts at slowing progression, to groundbreaking stem cell therapies developed right here in Sheffield. Stem cell treatment, in particular, has been transformative for patients, offering the most effective means of halting progression when started early.

Watching the incredible impact of these therapies - literally seeing a patient go from a wheelchair to playing football - remains one of the most profoundly moving moments of my life.

Although some of these treatments aren’t suitable for me personally, I’m proud to have contributed as a patient advocate, speaking at conferences and supporting the vital research Sheffield continues to lead.

The University’s pioneering work is not just advancing treatment for MS, but is also setting the stage for breakthroughs in other neurological conditions like Parkinson’s disease.

Watching the incredible impact of these therapies - literally seeing a patient go from a wheelchair to playing football - remains one of the most profoundly moving moments of my life. By supporting this vital work, we’re not just contributing to scientific progress: we’re investing in moments that change lives and shape the future of humanity."

Crucial support for global breakthroughs

Imagine a future where we can predict the progression of MS with precision thanks to advancements in AI, or where stem cell therapies offer groundbreaking new hope for devastating progressive diseases. These are no longer distant dreams but achievable goals, made possible through precisely the kind of research Sheffield excels at.

I remain deeply committed to raising awareness and funds for global MS brain health initiatives. In May 2025, I’ll embark on an ambitious 5,000-mile cycling challenge across Canada using a recumbent trike. This journey, shared on my platform theMSguide.com, will showcase the power of resilience - and the vital importance of funding world-class research like that being conducted at SITraN.

Together, we can be part of these transformative discoveries, ensuring Sheffield blazes a trail for the future as a true global leader in neuroscience innovation and impact.

By coming together to support this incredible work, we’re not just contributing to scientific progress: we’re investing in moments that change lives and shape the future of humanity.