Show simple item record

dc.contributor.authorLu, C-H
dc.contributor.authorPetzold, A
dc.contributor.authorKalmar, B
dc.contributor.authorDick, J
dc.contributor.authorMalaspina, A
dc.contributor.authorGreensmith, L
dc.descriptionPMCID: PMC3397981en_US
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.abstractBACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterised by progressive degeneration of motor neurons leading to death, typically within 3-5 years of symptom onset. The diagnosis of ALS is largely reliant on clinical assessment and electrophysiological findings. Neither specific investigative tools nor reliable biomarkers are currently available to enable an early diagnosis or monitoring of disease progression, hindering the design of treatment trials. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using the well-established SOD1(G93A) mouse model of ALS and a new in-house ELISA method, we have validated that plasma neurofilament heavy chain protein (NfH) levels correlate with both functional markers of late stage disease progression and treatment response. We detected a significant increase in plasma levels of phosphorylated NfH during disease progression in SOD1(G93A) mice from 105 days onwards. Moreover, increased plasma NfH levels correlated with the decline in muscle force, motor unit survival and, more significantly, with the loss of spinal motor neurons in SOD1 mice during this critical period of decline. Importantly, mice treated with the disease modifying compound arimoclomol had lower plasma NfH levels, suggesting plasma NfH levels could be validated as an outcome measure for treatment trials. CONCLUSIONS/SIGNIFICANCE: These results show that plasma NfH levels closely reflect later stages of disease progression and therapeutic response in the SOD1(G93A) mouse model of ALS and may potentially be a valuable biomarker of later disease progression in ALS.
dc.format.extente40998 - ?
dc.relation.ispartofPLoS One
dc.subjectAmyotrophic Lateral Sclerosis
dc.subjectDisease Models, Animal
dc.subjectDisease Progression
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectNeurofilament Proteins
dc.subjectSpinal Cord
dc.subjectSuperoxide Dismutase
dc.subjectSuperoxide Dismutase-1
dc.subjectTreatment Outcome
dc.titlePlasma neurofilament heavy chain levels correlate to markers of late stage disease progression and treatment response in SOD1(G93A) mice that model ALS.
dc.typeJournal Article
dc.relation.isPartOfPLoS One
dc.relation.isPartOfPLoS One
dc.relation.isPartOfPLoS One
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Neuroscience and Trauma

Files in this item


This item appears in the following Collection(s)

Show simple item record

Return to top