Image: Dr Lara McManus
Trinity College Dublin’s Dr Lara McManus explains her award-winning biomedical research which aims to improve outcomes for people living with motor neurone disease.
In Ireland, there are currently 420 people living with amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), with about 150 new diagnoses every year. Dr Lara McManus, a research assistant professor at the Academic Unit of Neurology in Trinity College Dublin (TCD), is developing methods that help with the diagnosis and treatment of this rare, neurological disease.
Having recently been awarded a Royal Society University Research Fellowship and a biomedical project grant from the Motor Neurone Disease Association, McManus’ latest project will use high-density electrode grids to examine the neuroelectric signalling between the brain and motor neurons in ALS patients.
On receiving the Royal Society Fellowship, McManus said she was “confident that the work will radically change the lives of people with ALS by speeding up the development of new and better drugs”.
McManus completed a PhD in electronic engineering with Prof Madeleine Lowery at University College Dublin (UCD). During her PhD, she spent time at the Rehabilitation Institute of Chicago where she began working with high-density electrode grids. This technology enables the electrical activity of motor units within the muscle to be identified using non-invasive recordings from the skin surface.
According to McManus, “This information is extremely useful for understanding motor function and neurodegenerative diseases, as motor neurons are the final pathway through which activation signals from the brainstem/spinal cord are transmitted to muscle. They provide the neural drive for all muscle movements”.
“I’m excited to start building my research team and investigating the full potential of these measures”, she said.
‘The idea of using engineering principles to understand the complex functioning of the brain and body really appealed to me’
Tell us about your current research.
During my postdoctoral work at UCD, I collaborated with Dr Bahman Nasseroleslami in the Academic Unit of Neurology at TCD, which is led by Prof Orla Hardiman.
Their group was doing really exciting work in ALS, and they had just recently found that novel subtypes of the disease could be identified by examining patterns in the brain waves of people with ALS.
At that time, my research focused on examining how the control of motor units in the muscle changes following a stroke and in Parkinson’s disease. I realised that the algorithms that I had been developing could have an important application in helping us to understand ALS, which is a disease that is characterised by lower motor neuron dysfunction.
By combining high-density EMG with recordings of brain waves (electroencephalography, EEG), we could examine the traffic of electrical activity from the brain to motor units to give a more complete picture of how the motor network is affected in ALS. We can use these recordings to identify disrupted neuroelectric signalling to the motor neurons, which will enable us to quantify aspects of the disease that cannot currently be measured or assessed.
Diagram of the neuroelectric signalling. Image: © Lara McManus
Estimates of motor unit connectivity could allow us to detect early signs of motor unit dysfunction and could also provide a quantitative tool to identify different ALS subtypes and measure disease progression.
The Academic Unit of Neurology is the ideal location to build my team, as it has an international reputation as a centre of excellence in ALS research. As part of the unit, I can also take full advantage of all the expertise within it and benefit from its established links with other centres of neurodegeneration in Europe and Canada.
Why is your research important?
ALS is a neurodegenerative condition characterised by loss of motor function, coupled with cognitive and behavioural changes. We now know that this loss of function is associated with changes in activation of specific brain networks, and as the disease progresses, with degeneration of these networks. One of the major challenges in identifying and testing new therapeutics for ALS is the absence of any quantitative measures to detect these changes in the motor network.
My research aims to provide a tool to measure brain-muscle function using direct estimates from motor units. The ability to measure these changes would give us a way of reliably testing the efficacy of different treatments in clinical trials. It could also aid in the design of clinical trials, by identifying motor network changes at an earlier disease stage and by providing us with a more effective way of identifying ALS subtypes. This would ensure that the right patients are receiving the right type of treatment at the right time.
What inspired you to become a researcher?
I don’t think there was any one moment of inspiration, it was more of a gradual realisation. I do remember enjoying school projects where I could pick my own topic and learn more about something I was really interested in.
During my undergraduate, I did two summer research internships in UCD and TCD in completely different areas. I really enjoyed both internships, but I think I was still undecided on whether a research career was for me.
Perhaps the spark happened when I realised what it was that I wanted to research.
I always loved problem-solving and the logical and practical approach of engineering, but for me the ‘pure’ engineering projects were missing a human element.
In my final year, I took a module on neural engineering and I realised that this was the field that I wanted to work in. The idea of using engineering principles to understand the complex functioning of the brain and body really appealed to me and I felt that in this field of research, I could make a tangible impact on our ability to understand and treat neurological diseases.
What are some of the biggest challenges or misconceptions you face as a researcher in your field?
I think with any new technology or methodology there will be some scepticism at the beginning. In my research field, it is extremely important for us to show how the markers we derive from the brain and muscle recordings relate to the underlying disease.
We need to examine our results in the context of each person’s clinical profile, working with clinicians and experts in other aspects of ALS (genetics, cognition, imaging). If we can show how markers we derive are linked with what we already know from clinical assessment, clinicians will have more confidence in the new information that our results can reveal.
It is also important to make it clear to clinicians that these measures will not replace clinician expertise, but rather they are intended as a quantitative tool to support clinical diagnosis and assessment.
ALS is a multifaceted disease that can vary hugely from person to person. Clinicians need new tools that are capable of capturing this heterogeneity so that they can give their patients more information on their individual prognosis.
Do you think public engagement with science has changed in recent years?
Overall, I would like to think that there is now a greater appreciation of how vital scientific research is and hopefully, more support for investing money in research. The pandemic has shown how much the scientific community can achieve when they come together towards a common goal, but what the public may not realise is that the vaccines were not just a few months of work, they were the result of decades of groundwork in mRNA research.
When it comes to research, we need long-term planning, funding, and vision to see what our current research ideas could lead to and the future problems they could address.
I am constantly looking for better ways to describe and present my research. For research engagement, it’s essential that the public can first understand what I am doing and why I am doing it.
Our research group in the Academic Unit of Neurology is very active in public engagement: we have a website (rmn.ie), social media profiles and a newsletter to make sure that people with ALS and their caregivers are kept up to date with our latest research. We are in regular contact with the Irish Motor Neurone Disease Association and work closely with the Irish National ALS Clinic, led by Prof Hardiman, to make sure that those living with ALS/MND are aware of the research and offered the opportunity to participate and contact the researchers with queries about the studies.
The unit is also involved in the recently launched Precision ALS programme, which has a strong focus on public and patient involvement in research.
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