267 Motor system biomarkers in amyotrophic lateral sclerosis. Issue 12 (14th November 2019)

• Record Type: Journal Article
• Authors: Edmond, Evan C; Menke, Ricarda; Proudfoot, Malcolm; Talbot, Kevin; Stagg, Charlotte J; Turner, Martin R
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 90:Issue 12(2019)
• Page Start: e63
• Page End: e63
• Publication Date: 2019-11-14
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-ABN-2.213
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Therapeutic options for the fatal neurodegenerative disorder ALS are urgently needed. Trials rely on blunt outcome measures such as survival because of a lack of objective markers of disease activity and progression. The C9orf72 hexanucleotide repeat expansion (HRE) is associated with 10% of all cases of ALS, bringing the near-future prospect of oligonucleotide therapeutic trials. The development of biomarkers will reduce trial duration and cost by providing more sensitive measures of disease-slowing and/or evidence of target engagement. ALS is consistently associated with cortical hyperexcitability (CE), based on transcranial magnetic paired stimulation (TMS) to induce short-interval cortical inhibition (SICI). This project builds on the potential shown by non-invasive neuroimaging to provide biomarkers in ALS. We develop functional neuroimaging biomarkers that reflect the phenomenon of CE, including markers of pre-symptomatic pathology. Affected ALS patients carrying the C9orf72 HRE and a group of asymptomatic carriers are studied using a combined functional MRI (FMRI and MRS) and neurophysiological (MEG) readout. This study offers novel non-invasive biomarkers based on a consistent neurophysiological mechanism in ALS to advance therapeutic development