Transforming access to Motor Neurone Disease clinical trials

MND is a fatal, rapidly progressing disease that affects the brain and spinal cord. The disease attacks the nerves that control movement so muscles no longer work, often leaving people locked in a failing body, unable to move, talk and eventually breathe. 

To be established across England, Wales and Northern Ireland, the new MND Research Nurse Network, with the first nurses expected to be in post by the end of 2024. The MND Association is also investing £5 million funding to support MND research.

Currently, access to MND trials depends on a number of factors such as how proactive a person is in seeking opportunities, the knowledge their health and social care team has of research trials, as well as where they live, as many clinical trials only take place in a small number of locations. 

The MND Association Research Nurse Network will bring equitable access, with the opportunity to take part in clinical research and trials part of each person’s holistic care.

Director of Research Development at the MND Association, Dr Brian Dickie MBE, spoke to NR Times to tell us more.

How did this funding come about and how will it help people into clinical trials?

This is something that I have been looking at for a number of years. For many years, the MND Association has provided funding for 22 Care Centres and networks, and we probably see at least 80% of people living with MND across England, Wales and Northern Ireland.

MND is a rapidly progressing disease and the survival rate is about 18 months on average from diagnosis. This means that timely coordinated multidisciplinary care is absolutely essential because the needs of people with MND are many and varied and often quite rapidly changing. 

The premise behind the Care Centres and networks really was to provide that tightly coordinated multidisciplinary care. Now, of course, the centre's do have another incredibly valuable research resource which is relatively large numbers of people with this relatively rare disease coming through the doors of the various clinics. It is a fantastic opportunity for conducting research. However, it hasn't been particularly well supported in the past and it's actually been done very much on a trial by trial basis. 

If there's a research study that comes along, the funders will put money in and then the lead centre will allocate to other centres that have said yet we're happy to participate. 

What we're looking at here is to develop the infrastructure across the network, of having these research nurses embedded within care, then that will make it more sustainable and help to attract more studies because you're not having to constantly rebuild and attract new staff. 

These centres have staff that are really receptive nurses that are really experienced in MND, as the key issue is that within the NHS, there is a research staff, however, they are quite generic and are not necessarily linked to a particular condition.

What we're looking to do here is help to upskill stuff in MND by having this dedicated network and really embedding research within this multidisciplinary care model. 

What is the current state of MND research and what lines of investigation are looking hopeful?

The other reason for doing this other than equity reasons, is that there has also been an explosion of new knowledge of MND in recent years. 

If you look at the number of scientific and medical publications, it has risen exponentially in the last couple of decades and has really moved over the past 25 years, to the forefront of neurodegenerative disease research. A lot of that has been driven by research into the genetics of MND. 

There's a genetic component to most neurodegenerative diseases. MND sits in that sweet spot where we know that, with about 10% of cases, there's a strong family history. 

Through genome sequencing, we've identified at least 30 genes now linked to the disease which gives a strong starting point, and we're now identifying new biochemical pathways that are going wrong within MND. 

In terms of treatment, we're seeing a shift towards drug discovery and drug development. One of the things the MND Association is doing in collaboration with other organisations, such as the government, is investing £50 million in MND research over the next few years. 

So the conveyor belt of interesting ideas coming out of the university labs is starting to fill up - which is another reason for creating the network.

A programme was also announced last year called Experts-ALS which is a new experimental medicine platform designed to accelerate progress of effective drug therapies. 

Amyotrophic lateral sclerosis (ALS) is the most common form of MND, making up around 95% of cases. The programme received the largest ever government award for an MND research project and it is going to be topped up by the charities with another £3 million to £4 million.

It is not a randomised placebo controlled trial, but instead it is looking to see whether a drug is changing disease progression.

Within the UK NMD Research Institute, which has been established off the back of the government's commitment, there are going to be drug selection committees to help to identify these the best candidates we want to bring to the clinic.

Is Artificial Intelligence (AI) utilised in this process?

We do utilise AI in various ways. In the academic labs, the AI at the moment is more linked to the clinical features of the disease, trying to stratify the patients into different subgroups. 

This is because, a little bit like cancer, cancer isn’t one disease it is many, and MND isn't one disease. It's many different variations of a theme, and the chances are that a particular drug or a combination of drugs will be more effective in some subgroups than others. 

So we're moving into more of an era of precision medicine. In fact, there's one good example of that at the moment that's being reviewed by NICE, which is a drug that specifically targets the genetic cause of MND in around 3% of patients. It effectively switches off or turns down the activity of the gene which is having a toxic effect and the results are so far looking incredibly promising.

What are currently the biggest barriers to MND research?

Currently, the key barrier is ensuring better biomarkers. We have neurofilaments which is good, but we probably need more specific biomarkers that tell us more about the different drugs that are going to be tested. 

We have biomarkers for different reasons, for example, diagnostic biomarkers. Currently a major issue is the length of time it takes between first symptoms and diagnosis. It is still taking about a year on average from a person seeing symptoms to getting a diagnosis of MND, and of course, it is only at that point that the treatment starts from a disease. 

This means that 12 months have gone past in a disease where survival can be 18 months from diagnosis, but people are already on that slippery slope. 

So, maybe it's not surprising that the drugs don't work. Maybe some of the drugs that have been tested in the past would have been effective, but they were given too late. So, we need to diagnose the disease faster and biomarkers are a part of that. 

We need biomarkers to help diagnose, biomarkers to predict how the disease is likely to progress, biomarkers of targeted engagement - which are biomarkers to see if a drug is working - and biomarkers of efficacy.

Given the genetic element of the condition, is there research looking at gene therapy for MND?

Gene therapy strategies are being pursued quite actively by the drug industry for some of the rare, inherited forms of the disease,and some work that we are co-funding with the University of Sheffield and a company is developing a gene therapy approach targeting the disease.

One of the things the Association does is organise the annual International Symposium on ALS and MND. We had 1300 scientists, neurologists and healthcare professionals come to Basel, Switzerland last December. There was a presentation about gene therapy for ALS. The neurologist actually brought a patient with him who has shown quite remarkable restoration of function. 

So, we might not see the light at the end of the tunnel yet but the train is heading in the right direction and it's picking up speed.