Researchers will systematically investigate and design therapeutic strategies to address diseases at an early stage.
Professor Juan Burrone (Centre for Developmental Neurobiology) and Dr Ivo Lieberam (Centre for Gene Therapy and Regenerative Medicine / Centre for Developmental Neurobiology) together with collaborators at University College London, have received funding from the Medical Research Council (MRC) and the Motor Neurone Disease Association (MND Association) to investigate an early disease pathology in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
ALS and FTD are devastating neurodegenerative diseases for which there are currently no cures. The mechanisms behind these diseases remain unclear, however, these diseases ultimately result in a complete degeneration of axons, part of the neurons that allow them to carry signals and transmit information to other cells.
Recent work has observed that at an earlier stage of the diseases, axons exhibit abnormal functions including hyperexcitability, abnormal plasticity and reduced synapse function. This project will investigate these early axonal pathologies to develop novel therapeutic strategies to restore axon function and establish its role in disease progression.
The researchers will develop human neuronal culture models carrying mutations found in patients with ALS and FTD. Researchers will then be able to use this system to characterise altered axon functions and investigate the specific molecular mechanisms behind the dysfunction. The final stage of the project will aim to restore normal neuronal activity and communication and potentially prevent neuronal cell death.
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.
Professor Juan Burrone, lead investigator for the project.
The project "Dissecting the early dysregulation of neuronal output in human neurons: an opportunity for a functional rescue of ALS/FTD" will be led by Professor Juan Burrone with co-leads Dr Ivo Lieberam and University College London's Professor Mala Shah, Dr Pietro Fratta, and Professor Wenhui Song.
