12/08/24
Professor Juan Burrone and Dr Ivo Lieberam have been awarded a prestigious grant by the Medical Research Council (MRC) and the Motor Neurone Disease Association (MND Association) for a programme of research into the mechanisms underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which often co-occurs with ALS. The Burrone and Lieberam labs, and the groups of their colleagues Prof Pietro Fratta, Prof Mala Shah and Prof Wenhui Song (all UCL), will systematically investigate the abnormal functional axonal output in ALS and FTD at both cellular and circuit levels. They hypothesise that restoring axon function could be a promising strategy for treating ALS and that motor neuron integrity could be reestablished by normalising neuronal excitability and synaptic function.
Juan Burrone, Professor of Developmental Neurophysiology in the Centre for Developmental Neurobiology and MRC Centre for Neurodevelopmental Disorders said:
“We are very grateful to the MRC and MND Association for funding our proposal. This is an exciting collaborative project that aims to understand the cellular pathologies behind ALS/FTD to identify a new therapeutic angle. We will focus on the early stages of the disease — before axons degenerate, but when their function is already compromised. Our aim is to rescue axon function in the hope of preventing neurodegeneration.”
Ivo Lieberam, Senior Lecturer in the Centre for Developmental Neurobiology, the Centre for Gene Therapy and Regenerative Medicine, and the MRC Centre for Neurodevelopmental Disorders said:
“This MRC Programme Grant will enable our team to approach potential treatments for ALS/FTD from a different angle: The key idea is that changes in gene expression at the early stage of the disease cause abnormal activation and communication of neurons, and that either correcting gene expression, or normalizing neuronal excitation, may stop or even revert the disease process.”
The MRC, a Council within the UKRI, is a government-funded body with the mission of improving human health through world-class medical research. Programme Grants are some of the Council’s larger awards and are extremely competitive. They provide support for a coordinated and coherent group of related projects with the aim of making a substantial contribution to human health. This is the second MRC Programme Grant in the Centre for Developmental Neurobiology and it will run until 2029.
Burrone and Lieberam’s grant will support research that aims to further our understanding of the causes of both ALS and FTD and use these insights to signal novel therapeutic targets. Their labs will work from the central hypothesis that axon function in neurons affected by ALS and FTD is disrupted early on in the course of the disease, and that this disruption is key to disease progression. In their programme of work, the labs will rescue the axonal dysfunction identified, yielding potential novel therapeutic targets for early in the disease progression.
ALS is a fatal neurodegenerative disease, characterised by the degeneration of motor neurons in both the brain stem and the spinal cord. There is currently no cure for the disease and patients suffer from progressive muscle weakness, eventually leading to paralysis and respiratory failure. The condition is relatively common with a lifetime risk of 1 in 300 and often co-occurs with FTD. Burrone and Lieberam’s programme will be an important stride towards understanding when and how we may be able to target therapies for these diseases.
Image credit: Federica Riccio, King's College London
