Identifying biomarkers of disease onset and progression for translation into early diagnosis and measures of efficacy in C9orf72-ALS/FTD clinical trials

Prof. Dame Pamela Shaw
PI Prof. Dame Pamela Shaw
Co-investigators Prof. Guillaume Hautebergue
Prof. Mimoun Azzouz
Dr Jonathon Foley
Dr Amanda Heslegrave
PI organisation University of Sheffield
Funding awarded £598,880
Completion date 31st October 2025 (18 months)

ALS/MND is a progressive neurodegenerative condition where the motor neurons, enabling movement through our muscles, die, causing disability in walking, talking, eating, and breathing. Average life expectancy is 2-3 years from symptom onset. Treatments to slow the loss of motor neurons are urgently needed.

An expanded section of DNA in the C9orf72 gene causes ALS/MND in 10% of cases. The expansion varies in size and produces 5 different toxic proteins that injure motor neurons to varying degrees, though their relative impacts are incompletely understood. Crucible is developing a potential treatment that stops toxic protein production and has plans to evaluate this in clinical trials. Using samples donated by patients and clinical data, we aim to develop tests to reliably measure the toxic proteins as biomarkers to rapidly demonstrate treatment effects and reduced motor neuron injury, aiming to accelerate the development of new treatments for people with C9orf72-MND.

Prof. Dame Pamela Shaw