Development of a fluid biomarker for C9orf72 antisense repeat-derived proteins

Prof. Adrian Isaacs
PI Prof. Adrian Isaacs
Co-investigators Dr Amanda Heslegrave
Prof. Henrik Zetterberg
Prof. Andrea Malaspina
Prof. Jonathon Rohrer
PI organisation University College London & UK DRI
Funding awarded £560,432
Completion date 31st March 2026 (21 months)

A mutation in the C9orf72 gene is the most common known cause of ALS. The C9orf72 mutation generates two types of damaging proteins, termed ‘sense’ and ‘antisense’ proteins. Recently two clinical trials that reduced only the levels of the sense proteins failed to show any benefit for C9orf72-ALS patients. This suggests that we also need to target the antisense proteins to successfully treat C9orf72-ALS. However, we currently have no way to measure the amount of antisense proteins. Without a test to measure the antisense proteins, it will not be possible to tell whether a drug has successfully reduced these proteins, which is a barrier to starting clinical trials with promising new drugs. We therefore plan to develop a test that can measure the amount of antisense proteins and can be used in clinical trials, greatly facilitating our ability to test new drugs and find a treatment for C9orf72-ALS.

Prof. Adrian Isaacs