Related Experiment Video
Updated: Jun 15, 2026
05:16
Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides
Published on: May 7, 2020
6.9K
Design considerations for C9orf72 disease prevention trials
Michael Benatar1, Adam M Staffaroni2, Joanne Wuu1
1Department of Neurology and the ALS Center, Miller School of Medicine, University of Miami, Miami, FL 33129, USA.
Brain : a Journal of Neurology
|August 12, 2025
Summary
Preventing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is now feasible. A C9orf72 gene expansion affects 10% of ALS and 15% of FTD cases, offering a target for early intervention in at-risk individuals.
Area of Science:
- Neuroscience and Genetics
- Neurodegenerative Disease Research
Background:
- The C9orf72 gene hexanucleotide repeat expansion is a significant genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
- This expansion accounts for approximately 10% of ALS and 10-15% of FTD cases, often presenting with overlapping or distinct clinical syndromes.
- Clinically unaffected carriers of this expansion represent the largest identifiable population at high risk for developing ALS and/or FTD, making them a key target for preventive strategies.
Purpose of the Study:
- To unify efforts in designing disease prevention trials for individuals at elevated genetic risk due to C9orf72 repeat expansions.
- To establish a collaborative framework involving ALS, FTD, and C9orf72 carrier communities, regulatory bodies, and drug developers.
- To outline recommendations for critical aspects of prevention trial design, including outcome measures, eligibility, biomarkers, and regulatory considerations.
Main Methods:
- Convened a multi-stakeholder workshop supported by The Association for Frontotemporal Degeneration and The ALS Association in June 2024.
- Focused on developing unified strategies for prevention trials targeting the C9orf72 repeat expansion's phenotypic spectrum.
- Synthesized recommendations on outcome measures, eligibility criteria, biomarker utilization, digital health technologies, analytical frameworks, and regulatory pathways.
Main Results:
- Identified shared clinical and biological markers for quantifying pre-symptomatic disease progression across the ALS/FTD spectrum.
- Emphasized the need to move beyond siloed approaches and consider the full spectrum of C9orf72-related neurodegeneration.
- Generated consensus on key elements required for designing effective prevention trials in at-risk C9orf72 expansion carriers.
Conclusions:
- Prevention of C9orf72-related ALS and FTD is an achievable goal, particularly in asymptomatic carriers.
- Collaborative, unified approaches are essential for successful prevention trial design and execution.
- The current understanding and enthusiasm warrant immediate action to design and implement C9orf72 disease prevention trials.
