Biomarkers for C9orf7-ALS in Symptomatic and Pre-symptomatic Patients: State-of-the-art in the New Era of Clinical Trials - Sorbonne Université Access content directly
Journal Articles Journal of Neuromuscular Diseases Year : 2022

Biomarkers for C9orf7-ALS in Symptomatic and Pre-symptomatic Patients: State-of-the-art in the New Era of Clinical Trials

Abstract

The development of new possible treatments for C9orf72-related ALS and the possibility of early identification of subjects genetically at risk of developing the disease is creating a critical need for biomarkers to track neurodegeneration that could be used as outcome measures in clinical trials. Current candidate biomarkers in C9orf72-ALS include neuropsychology tests, imaging, electrophysiology as well as different circulating biomarkers. Neuropsychology tests show early executive and verbal function involvement both in symptomatic and asymptomatic mutation carriers. At brain MRI, C9orf72-ALS patients present diffuse white and grey matter degeneration, which are already identified up to 20 years before symptom onset and that seem to be slowly progressive over time, while regions of altered connectivity at fMRI and of hypometabolism at [18F]FDG PET have been described as well. At the same time, spinal cord MRI has also shown progressive decrease of FA in the cortico-spinal tract over time. On the side of wet biomarkers, neurofilament proteins are increased both in the CSF and serum just before symptom onset and tend to slowly increase over time, while poly(GP) protein can be detected in the CSF and probably used as target engagement marker in clinical trials.
Fichier principal
Vignette du fichier
jnd_2022_9-1_jnd-9-1-jnd210754_jnd-9-jnd210754.pdf (735.08 Ko) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

hal-03538900 , version 1 (21-01-2022)

Identifiers

Cite

Giorgia Querin, Maria Grazia Biferi, Pierre-Francois Pradat. Biomarkers for C9orf7-ALS in Symptomatic and Pre-symptomatic Patients: State-of-the-art in the New Era of Clinical Trials. Journal of Neuromuscular Diseases, 2022, 9 (1), pp.25-37. ⟨10.3233/JND-210754⟩. ⟨hal-03538900⟩
89 View
109 Download

Altmetric

Share

Gmail Facebook X LinkedIn More