Researchers develop new approach to target cells affected by motor neurone disease
Researchers from the Francis Crick Institute and the UCL Queen Square Institute of Neurology have found a way to selectively target cells affected by motor neurone disease (MND). Published in the journal Science, the study details how the team developed DNA molecules that contain ‘invisibility cloak’ sequences, which can only be removed by diseased cells.
It is hoped that preventing healthy cells from reading the molecules’ messages could lead to safer and more effective gene therapies for MND, as well as other neurodegenerative diseases, including frontotemporal dementia.
“While neurodegenerative diseases have devastating effects, we can estimate that less than 0.00001% of cells in a patient’s body are actually diseased,” explained study lead Oscar Wilkins. “The challenge is finding a way to specifically target treatments to this minuscule fraction of diseased cells, while avoiding unnecessary treatment of the 99.99999% of cells which are healthy,” he said.
Affecting up to 5,000 adults in the UK at any one time, MND is a rare condition that progressively damages parts of the nervous system and leads to muscle weakness, often with visible wasting.
The team’s new approach centres around the activity of the TDP-43 protein, which resides near the DNA in healthy cells and helps them to correctly interpret the DNA’s genetic instructions. However, this protein gets stuck in distant parts of diseased cells, corrupting their interpretation of genetic messages.
Using artificial intelligence prediction tools and careful design, the researchers created DNA sequences that behave in the opposite way – the messages from the DNA are corrupted in healthy cells, but can be interpreted correctly in diseased ones.
US collaborators from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development also contributed to the therapeutic approach.
Work to further develop gene therapies for amyotrophic lateral sclerosis, the most common form of MND, using the system is being supported by the Crick Translation Fund and by the UCL Neurogenetics Therapy Programme.
