One of the core mysteries of ALS that we still need to solve is why the disease differs from person to person, what we call heterogeneity. A better understanding of different forms of ALS will allow for more effective and efficient clinical trials of experimental treatments and will pave the way towards a day when we can offer a more personalized medicine approach, where an individual’s treatment regimen would be specific to them. A great example would be cancer, where present-day treatments differ greatly depending on the location and type someone has.
Dr. Stefan Dukic, a postdoctoral researcher at University Medical Centre Utrecht (UMC Utrecht) in The Netherlands, has been developing a non-invasive way to subgroup people with ALS far better than current methods using clinical observation and amazingly, it may be possible for individuals before symptom onset. A method called resting-state electroencephalogram (EEG) uses simple brain electrodes placed on the scalp to measure the brain’s electrical activity. Dr. Dukic, along with colleagues at world-leading clinical centres in Dublin, Ireland, and Utrecht, and under the co-supervision of Profs. Orla Hardiman and Leonard van den Berg, at respective institutions, demonstrated for the first time that EEG can capture abnormal patterns of motor and cognitive brain activity in ALS and that these patterns revealed four distinct clusters across the people studied. Surprisingly, these clusters also correlated with distinct clinical profiles and disease trajectories, indicating that EEG-detected brain patterns may be able to predict how someone’s ALS will progress. This exciting initial work was published in the journal Brain in 2022.
Dr. Dukic is now poised to evolve his EEG work closer toward potential use in practice and to see how it might have additional, perhaps even better, application in ALS. The next steps involve strengthening the power of EEG by combining it with another non-invasive technique, magnetic resonance imaging (MRI), to form a combination measurement. He also aims to use this combination measurement to look for pre-symptomatic markers of ALS by studying asymptomatic family members of individuals with ALS who carry known hereditary genetic variants and comparing them to data from controls and people already diagnosed.
A Stevie Fever Foundation-ALS Canada Acceleration Grant was awarded to provide personnel support to drive this work forward faster by recruiting participants, collecting data, and analyzing results at more than twice the speed Dr. Dukic can currently maintain. He also aims to greatly increase the size of the study compared to his originally published work in 2022. This would enhance the reliability of results, particularly when discovering sensitive patterns in individuals with underlying disease processes beginning but not yet experiencing any symptoms.
“Finding innovative ways to detect the earliest signs of disease, long before symptoms begin, could be the key to someday preventing ALS as we know it today. Providing support to accelerate discovering if this non-invasive strategy can detect underlying pathology and potentially lead to earlier diagnosis and treatment is exactly the type of exciting opportunity this program was created for,” says Dr. David Taylor, Vice-President, Research and Strategic Partnerships, ALS Canada.
Contributing to the global ALS landscape
Dr. Dukic aims for EEG to be used in ALS far beyond The Netherlands and Ireland. His results from 2022 will undoubtedly spark confirmatory work in other countries and may stimulate others to study its potential in asymptomatic genetic variant carriers. EEG is widely available and relatively inexpensive to perform, and with that comes collaboration, something Trinity College and UMC Utrecht already do very well across Europe. Colleagues in Ireland, Prof. Roisin McMackin, Prof. Bahman Nasseroleslami and others are also exploring the utility of EEG in other ways.
Uniquely, Canada has the most detailed MRI data on ALS in the world, thanks to the Canadian ALS Neuroimaging Consortium (CALSNIC) and CAPTURE (Comprehensive Analysis Platform To Understand, Remedy, and Eliminate) ALS initiatives led by Dr. Sanjay Kalra at the University of Alberta. EEG has not been incorporated into any of the Canadian ALS studies, but establishing a joint EEG-MRI measure through the Acceleration Grant could yield strong future collaborations here and a potential to embrace its value earlier than in other regions.
It’s still early to know the full value of EEG and EEG-MRI in ALS and whether it will ultimately provide human impact. This funding will help Dr. Dukic find that out faster, which is no small thing for ALS.