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Identifying early disease markers of amyotrophic lateral sclerosis

Project details

Researcher
Dr Chris Black
Institute
UCL Queen Square Institute of Neurology
Research area
Motor neurone disease
Funding type
Fellowship
Awarded in
May 2023
Completion
Ongoing

The Brain Research UK Miriam Marks Research Fellowship scheme was established in 2020 in partnership with UCL Queen Square Institute of Neurology. The scheme is funded by the Miriam Marks Endowment Fund, which was established by the family of Mrs Miriam Marks in 1971 to support research into brain degeneration.

This award to Dr Chris Black is one of two Fellowships awarded in 2023, and will support his research into motor neurone disease.

About Dr Chris Black

With a PhD in Biomedical Engineering from Brown University in the United States, Chris remained at Brown as a post-doc, carrying out research focused on the neural mechanisms of pain.

He now brings this engineering and neuroscience background to the study of neurodegenerative diseases. His overarching scientific goal is to combine engineering, neuroscience and computational approaches to elucidate the brain mechanisms underlying neurodegenerative disease and neurological dysfunction, to advance diagnosis and therapy.

This Fellowship enables him to pursue this line of research under the supervision of Professor Rob Brownstone, whose laboratory at UCL is at the forefront of motor neuroscience. His group utilises state-of-the-art techniques to investigate the neural and behavioural characteristics associated with neurodegeneration.

Chris will receive first-hand expert training in advanced neuroscientific methodologies to examine motor control and neurodegeneration.

About ALS

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neurone disease. It is a fatal, rapidly-progressing disease that attacks motor neurones, the nerves in the spinal cord and brain that control muscle activity - including the muscles responsible for breathing, swallowing speaking, walking and gripping. As these nerves are attacked, messages gradually stop reaching the muscles. This initially leads to weakening and wasting and then, eventually severe paralysis and breathing difficulties.

There is no cure for ALS, it is always fatal, but there are treatments available that can extend life expectancy and improve quality of life. However, by the time the disease is typically diagnosed, it has already caused significant and irreversible damage.

Delayed diagnoses are due to a lack of well-defined behavioural and biological markers of early-stage neurodegeneration. Chris's research aims to address this.

Identifying early disease markers of ALS

In his PhD research, Chris focused on understanding how sensory areas of the brain process information during chronic pain. He realised that similar changes to those observed in many of the neural circuits within these sensory areas during chronic pain were implicated in motor areas of the brain during ALS. These are the 'motor' circuits that enable us to control movement voluntarily. Although these circuits have been well-studied, little is known about what happens to them in the long-term in the context of neurodegenerative disease. This is important in the context of ALS, as there is a need to act as quickly as possible to slow the damage.

Patients with ALS often experience a delay between the initial onset of symptoms and diagnosis. Chris wants to establish whether there is any way to identify the abnormal activity in neural circuits early on, before symptoms present. Using mouse models of ALS, he will look at standard behaviours that we expect to see in ALS and see how the onset of these behaviours maps to changes in brain activity. The idea is that this information can then be used to develop neurological biomarkers that can be used to diagnose ALS earlier than is currently possible.

He will use new behavioural and neurological recording techniques to enable constant, detailed monitoring of behaviour and brain activity, going beyond the standard practice of monitoring the animals only during experiments. He will aim to pinpoint the first behavioural changes and map these to early changes in brain activity, and see how these dynamics evolve as the disease progresses.

Impact

Although there is no cure for ALS, there are treatments that can improve life expectancy and quality of life. It is vital that these treatments are started as early as possible.

Chris's research could ultimately be used to develop tools that could pick up signs of the disease early in the disease process. A better understanding of disease processes will also give a better insight into how to treat the disease.

Chris will benefit from exposure to the world's strongest department investigating degenerative neuromuscular disease, and from access to the state-of-the-art facilities, and the opportunity to collaborate with like-minded researchers throughout the department. This will enable him to succeed in his research and contribute meaningfully to our scientific understanding of neurodegenerative disease.

"With his background, skillset and creativity, Chris is a scientist who can contribute to the discovery of biological mechanisms underlying neurodegeneration. His research proposal integrates engineering, neuroscience, and computational approaches to investigate behavioural and neural correlates of ALS, a disease that we are studying in the lab and that is a strength in our department." Professor Rob Brownstone

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