C9orf72 associated motor neurone disease (MND): investigating the genetic penetrance, expressivity, metabolic and inflammatory clinic-ready biomarkers

Dr Arianna Tucci
PI Dr Arianna Tucci
Co-investigators Dr Alexander Murley
Prof. Henry Houlden
Prof. Andrea Malaspina
Prof. Henrik Zetterberg
Collaborators Prof. Pietro Fratta
PI organisation Queen Mary University of London
Funding awarded £670,046
Completion date 30th November 2025 (18 months)

Finding a treatment that slows down MND progression depends on our understanding of those factors that contribute to the initiation and progression of disease. The discovery of mutations in the C9orf72 gene in a percentage of individuals with MND and in others that develop frontotemporal dementia, as the commonest genetic cause of these disorders, has reinvigorated the search for “disease modifiers”: the molecular changes that alter disease progression and the clinical presentation. The fact that people with C9orf72 sometimes do not develop disease is also of great importance, for genetic counselling and for clinical trials. Addressing these questions has been challenging due to lack of genetic and clinical information on large populations. We will use the power of UK Biobank, a collection of genetic and clinical information on 500,000 people, and utilise the latest genomic and biomarker technology to investigate large C9orf72 cohorts at UCL, QMUL and Cambridge to address these fundamental questions.

Dr Arianna Tucci