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First study to examine the functional connectivity between the brain and motor units in ALS

Dr Lara McManus, Research Fellow, from the Academic Unit of Neurology at the School of Medicine, Trinity College Dublin has been awarded a Royal Society University Fellowship to detect early signs of motor unit dysfunction in ALS and to quantitatively measure the disease progression. Royal Society Research Fellowships are awarded to outstanding scientists who are in the early stages of their research career and have the potential to become leaders in their field.

Motor Neuron Disease, also known as amyotrophic lateral sclerosis (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 progression, with degeneration of these networks. One of the major challenges in therapeutics is the absence of quantitative measures to detect very early network disruption.

No method currently exists however to detect early network disruption or to quantitatively measure disease progression and this presents a major challenge in the treatment and care of patients. In Ireland, there are currently 420 people living with ALS, with 150 new diagnoses every year.

Lara’s work aims to explore a novel technology to provide new markers of disrupted neuroelectric signalling that can detect early signs of motor unit dysfunction and provide a quantitative measure of both different subtypes of disease, and of disease progression within subgroups of those with ALS.

Speaking about her award, Lara said:

The Society University Fellowship Award combines my background in engineering with cutting edge clinical neuroscience. This will bring an entirely new dimension to how we study ALS. I am confident that this work will radically change the lives of people with ALS by speeding up the development of new and better drugs”.

Lara’s work will develop a quantitative tool to assess dysfunction of the motor network in ALS. High density electromyography will be used to record directly from motor units in the muscle, and combined with recordings of brain waves (electroencephalography, EEG) to measure traffic of electrical activity between the brain and muscle.

Lara had previously worked with high density arrays as a research scholar in the Rehabilitation Institute of Chicago and later brought this methodology back to Ireland. Over the last ten years, she has used this technology to gain a window into the nervous system and study motor control in stroke and in Parkinson’s disease. Her recent research has focused on developing novel methods for extracting information from high density EMG. These methods of examining motor unit connectivity and action potential morphology are particularly relevant for studying the changes that occur in ALS.

Speaking about this prestigious and generous funding for ALS research, Lara’s mentor and one of world’s leading authorities on ALS, Professor Orla Hardiman, Professor of Neurology & Head of the Academic Unit of Neurology, Trinity College Dublin, said:

Lara is exactly the type of person we need on ALS research. Coming from a background in electrical engineering, she brings new perspectives to how we think about the changes in electrical signals in ALS. Her transformative work will drive the development of precision-medicine based markers of disease that we can incorporate into clinical trials that are designed to ensure that the right patient receives the right drug at the right time”.

Dr Lara McManus, Research Fellow, from the Academic Unit of Neurology at the School of Medicine, Trinity College Dublin