In our third 'Meet the researcher' post, we talk to Professor Volker Straub, Professor of Neuromuscular Genetics at Newcastle University. He trained as a paediatric neurologist at the University of Dussledorf and the University of Essen, Germany, and then completed his PhD on Duchenne muscular dystrophy. He leads the John Walton Muscular Dystrophy Research Centre, and is Deputy Lead for the NIHR Newcastle Biomedical Research Centre’s (BRC) Neuromuscular Disease theme.
I trained as a medic and then did a PhD in Duchenne muscular dystrophy; the most common and best characterized of all neuromuscular diseases. I then applied for a postdoctoral position in the US to gain some more experience in basic medical research. After finishing this, I continued to focus my clinical work in this area and specialised in paediatrics and paediatric neurology.
Our team here at the John Walton Muscular Dystrophy Research Centre (JWMDRC) is focusing on both translational research in the pre-clinical field; looking at gene discovery and understanding disease mechanisms, as well as clinical research; discovering more about the natural history of diseases and doing more interventional clinical trials. It is a really exciting time, as we are starting to develop treatments for progressive genetic diseases, which around 20 years ago did not have such outcomes. In the past, after patients were diagnosed, the advice was just to stay at home. Now, patients can actively get involved in trials and help us understand disease diagnostics, while getting treatments that can significantly improve quality of life. For patients, what matters most is their quality of life. Curing a degenerative disease is very difficult, so many of our patients would be happy if you could stop disease progression through treatments.
What has changed the most in the past few years is the role of digital technologies; the application of high throughput screening of large amounts of genetic data and the computer analysis of that data. We see this more and more; computers have changed the way we do research. Another change is in the research services, particularly in co-located facilities, for example research services that are now commercial, and many different services coming together on one study.
Genetic neuromuscular diseases are very rare, so building robust and well-defined patient cohorts is incredibly important for sites like ours to be involved in clinical trials, whether it's natural history to understand the disease, or interventional clinical trials. Patient cohorts can also help to engage industry and encourage investment in drug development. The questions that industry would ask are: how many patients are there? How well do you understand the disease? Or how do you assess the disease? We are working closely with patients who have a genetic diagnosis on outcome measures of assessment, which need to be standardised for the application in clinical trials.
It is vital that we build up enough data of this kind to better understand disease progression. Because we are working with rare diseases, collaboration with different sites is very important to us too, as it allows us to reach more patients. This is where the NIHR Newcastle BRC adds value; we work very closely with other hospitals across the country who have a department focussing on neuromuscular diseases. Industry values these networks and partnerships between researchers and care providers, and well-defined data that can only be gathered by working closely together.
We have established very close partnerships with industry, both in our diagnostic research activities, our clinical trial activities. We also see it more and more often in the implementation of approved treatments into clinical practice. For diagnostics, pharmaceutical companies working in rare diseases are dealing with some of the most expensive drugs in the world. Because of this, every single diagnosed patient counts, and this is where we can help. We have the diagnostic expertise and can provide diagnostic testing. Again, this is why it is so important to have well-defined cohorts of patients. This is a prerequisite when it comes to clinical trials.
The JWMDRC owes its origins to Lord Walton, who established neuromuscular research in Newcastle in the 1950s. From here, it very quickly became an international centre of expertise and excellence, and trained neurologists from all over the world. We have the privilege that we can see both kids and adults; from babies to 100 year olds. Because our neuromuscular team is the only one in the northern region, our catchment area is very big; from the East to the West Coast, and from the Scottish borders down to North Yorkshire. We have clinics throughout the whole of the North of England, as well as in Newcastle.
In terms of the NIHR Newcastle BRC, we are working very closely with the mitochondrial team. Many of our patients share similar clinical symptoms, such as muscle wasting and weakness. Working together within the Newcastle BRC provides a great opportunity to share expertise and to learn from each other. We also benefit from the research infrastructure that the Newcastle BRC supports, as well as things like trial coordination, bio-banking and patient registries.
The Newcastle BRC focusses on ageing and long term conditions, and many of our genetic neuromuscular diseases are indeed long term conditions. Because of the progressive muscle wasting we see in many of our patients, the diseases provide an interesting model for some aspects of ageing research in Newcastle. One of the Newcastle BRC’s key interests is in sarcopenia, which is the loss of muscle mass in older people. Muscle wasting diseases are valuable when learning more about sarcopenia, and so our relationship with the BRC is very useful.
All of our patients have muscle weakness and in many cases this weakness also affects the respiratory or heart muscles. This makes them all high risk and we asked them to shield since the beginning of the pandemic, so we weren't able to see patients face to face for quite some time. We have done many more remote assessments for patients, which has been positive, and patients have been very grateful that they can continue being seen in some way, as it’s important to provide regular treatment of course, but also ongoing advice.
Mostly in novel therapies and also in how we assess patients. Following up from our previous discussion on COVID-19 and remote assessment, I do feel that for patient assessment in general, we will see a lot of change. I mentioned that our catchment area is very large and we have a clinic in Whitehaven that we normally drive to as a team of six. Perhaps now we could do this remotely. And when it comes to good, validated data, it would be interesting to see how we can assess people remotely using digital biomarkers.
Also, I think we’ll see a lot of change in treatment and clinical trials. I mentioned that only 20 years ago it was hard to believe that we could effectively treat a degenerative genetic disease. However, we are now involved in gene replacement therapy trials with some amazing outcomes. We are going to start at least two more gene therapy trials this year, and I would expect that gene editing with CRISPR-Cas would come to the clinic next year.