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A PET-CT study on neuroinflammation in Huntington’s patients participating in a randomised trial with laquinimod

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Title: A PET-CT study on neuroinflammation in Huntington’s patients participating in a randomised trial with laquinimod
Authors: Roussakis, A
Gennaro, M
Gordon, MF
Reilmann, R
Borowsky, B
Rynkowski, G
Lao-Kaim, NP
Papoutsou, Z
Savola, J-M
Hayden, MR
Owen, DR
Kalk, N
Lingford-Hughes, A
Gunn, RN
Searle, G
Tabrizi, SJ
Piccini, P
Item Type: Journal Article
Abstract: Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington’s disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis in vivo and explore the effects of laquinimod treatment. This study relates to the LEGATO-HD, multi-centre, double-blinded, Phase 2 clinical trial with laquinimod (US National Registration: NCT02215616). Fifteen patients of the UK LEGATO-HD cohort (mean age: 45.2 ± 7.4 years; disease duration: 5.6 ± 3.0 years) were treated with laquinimod (0.5 mg, N = 4; 1.0 mg, N = 6) or placebo (N = 5) daily. All participants had one 11C-PBR28 PET-CT and one brain MRI scan before laquinimod (or placebo) and at the end of treatment (12 months apart). PET imaging data were quantified to produce 11C-PBR28 distribution volume ratios. These ratios were calculated for the caudate and putamen using the reference Logan plot with the corpus callosum as the reference region. Partial volume effect corrections (Müller–Gartner algorithm) were applied. Differences were sought in Unified Huntington’s Disease Rating Scale scores and regional distribution volume ratios between baseline and follow-up and between the two treatment groups (laquinimod versus placebo). No significant change in 11C-PBR28 distribution volume ratios was found post treatment in the caudate and putamen for both those treated with laquinimod (N = 10) and those treated with placebo (N = 5). Over time, the patients treated with laquinimod did not show a significant clinical improvement. Data from the 11C-PBR28 PET-CT study indicate that laquinimod may not have affected regional translocator protein expression and clinical performance over the studied period.
Issue Date: 3-Apr-2023
Date of Acceptance: 25-Jan-2023
URI: http://hdl.handle.net/10044/1/102865
DOI: 10.1093/braincomms/fcad084
ISSN: 2632-1297
Publisher: Oxford University Press
Start Page: 1
End Page: 10
Journal / Book Title: Brain Communications
Volume: 5
Issue: 2
Copyright Statement: © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Publication Status: Published
Article Number: fcad084
Online Publication Date: 2023-04-03
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Department of Brain Sciences