MSA Trust funded research
Research results from MSA Trust-funded research
Practical Neurology Journal article ‘Multiple System Atrophy‘ – This is a practical guide to diagnosing and managing multiple system atrophy (MSA). We explain the newly published Movement Disorders Society Consensus Diagnostic Criteria, which include new ‘Clinically Established MSA’ and ‘Possible Prodromal MSA’ categories, hopefully reducing time to diagnosis. We then highlight the key clinical features of MSA to aid diagnosis. We include a list of MSA mimics with suggested methods of differentiation from MSA. Lastly, we discuss practical symptom management in people living with MSA, including balancing side effects, with the ultimate aim of improving quality of life.
A study led by Dr Viorica Chelban with co-author Professor Henry Houlden (both UCL Queen Square Institute of Neurology) has shown that a single biomarker can accurately measure the progression and response to treatment in people with Multiple System Atrophy
Structural and metabolic correlates of neuropsychological profiles in multiple system atrophy and Parkinson’s disease Kübler_Kobylecki_et_al_2023 (003)
Lay advisor to the MSA Trust Scientific advisory panel, John Telford, summarises the 2021-22 Research Grant projects in the three blog posts below:
2019/20: Dissecting the role of the Autophagy-lysosome pathway (ALP) in Multiple System Atrophy pathogenesis, £150,000 awarded to Dr Maria Xilouri of the Biomedical Research Foundation of the Academy of Athens
Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease. Piras IS, Bleul C, Schrauwen I, Talboom J, Llaci L, De Both MD, Naymik MA, Halliday G, inclusions Bettencourt C, Holton JL, Serrano GE, Sue LI, Beach TG, Stefanova N, Huentelman MJ. Acta Neuropathol Commun. 2020 Jun 3;8(1):76MOBP and HIP1 in multiple system atrophy: New α-synuclein partners in glial cytoplasmic implicated in the disease pathogenesis. Bettencourt C, Miki Y, Piras IS, de Silva R, Foti SC, Talboom JS, Revesz T, Lashley T, Balazs R, Viré E, Warner TT, Huentelman MJ, Holton JL. Neuropathol Appl Neurobiol. 2020 Dec 23. doi: 10.1111/nan.12688. Online ahead of print
Epigenomics and transcriptomics analyses of multiple system atrophy brain tissue supports a role for inflammatory processes in disease pathogenesis. Bettencourt C, Piras IS, Foti SC, Talboom J, Miki Y, Lashley T, Balazs R, Viré E, Warner TT, Huentelman MJ, Holton JL. Acta Neuropathol Commun. 2020 May 14;8(1):71
White matter DNA methylation profiling reveals deregulation of HIP1, LMAN2, MOBP, and other loci in multiple system atrophy. Bettencourt C, Foti SC, Miki Y, Botia J, Chatterjee A, Warner TT, Revesz T, Lashley T, Balazs R, Viré E, Holton JL. Acta Neuropathol. 2020 Jan;139(1):135-156
Exploring the putative role of kallikrein-6, calpain-1 and cathepsin-D in the proteolytic degradation of α-synuclein in multiple system atrophy. Kiely AP, Miners JS, Courtney R, Strand C, Love S, Holton JL. Neuropathol Appl Neurobiol. 2019 Jun;45(4):347-360
Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson’s disease. Foti SC, Hargreaves I, Carrington S, Kiely AP, Houlden H, Holton JL. Sci Rep. 2019 Apr 25;9(1):6559. doi: 10.1038/s41598-019-42902-7
2018: Professor Janice Holton Professor in Neuropathology, Director of Neuropathology, Queen Square Brain Bank, UCL Institute of Neurology, awarded £129,270 for ‘Understanding selective brain regional vulnerability in multiple system atrophy’
Immunohistochemical and Molecular Investigations Show Alteration in the Inflammatory Profile of Multiple System Atrophy Brain. Kiely AP, Murray CE, Foti SC, Benson BC, Courtney R, Strand C, Lashley T, Holton JL. J Neuropathol Exp Neurol. 2018 Jul 1;77(7):598-607
Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients. Schottlaender LV, Bettencourt C, Kiely AP, Chalasani A, Neergheen V, Holton JL, Hargreaves I, Houlden H. PLoS One. 2016 Feb 19;11(2):e0149557
2015: Professor Janice Holton Professor in Neuropathology, Director of Neuropathology, Queen Square Brain Bank, UCL Institute of Neurology, awarded £124,440, ‘Understanding the degradation of alpha-synuclein protein in Multiple System Atrophy’
Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation. Kiely AP, Ling H, Asi YT, Kara E, Proukakis C, Schapira AH, Morris HR, Roberts HC, Lubbe S, Limousin P, Lewis PA, Lees AJ, Quinn N, Hardy J, Love S, Revesz T, Houlden H, Holton JL. Mol Neurodegener. 2015 Aug 27;10:41. doi: 10.1186/s13024-015-0038-3.
Alpha-synuclein mRNA expression in oligodendrocytes in MSA. Asi YT, Simpson JE, Heath PR, Wharton SB, Lees AJ, Revesz T, Houlden H, Holton JL. Glia. (2014) 2014 Jun;62(6):964-70
2013: Dr Janice Holton, Honorary Consultant and Reader in Neuropathology at UCL Institute of Neurology. Awarded £62,441 for the study of ‘The role of CoQ2 in multiple system atrophy’.
α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy? Kiely AP, Asi YT, Kara E, Limousin P, Ling H, Lewis P, Proukakis C, Quinn N, Lees AJ, Hardy J, Revesz T, Houlden H, Holton JL Acta Neuropathol. (2013) May;125(5):753-694
Identification and quantification of oligodendrocyte precursor cells in multiple system atrophy, progressive supranuclear palsy and Parkinson’s disease. Ahmed Z, Asi YT, Lees AJ, Revesz T, Holton JL. Brain Pathol. (2013) May;23(3):263-734
2012: Dr Janice Holton, Honorary Consultant and Reader in Neuropathology at UCL Institute of Neurology. Awarded £100,000 for the project ‘Neuroinflammation in multiple system atrophy: A neuropathological study’ (a 2 year study).
Review: The neuropathology, pathophysiology and genetics of multiple system atrophy. Ahmed Z, Asi YT, Sailer A, Lees AJ, Houlden H, Revesz T, Holton JL. Neuropathol Appl Neurobiol. (2012) 38(1):4-2
Neuropathology underlying clinical variability in patients with synucleinopathies. Halliday GM, Holton JL, Revesz T, Dickson DW. Acta Neuropathol. (2011)Aug;122(2):187-204
2009: Dr Janice Holton awarded £179,502 to study ‘Central Role of Oligodendroglia in pathogenesis of multiple system atrophy’.
Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. O’Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton JL, Revesz T, Lees AJ. (2008) Brain. 2008 131:1362-1372
LRRK2 and parkin immunoreactivity in multiple system atrophy inclusions. Huang Y, Song YJ, Murphy K, Holton JL, Lashley T, Revesz T, Gai WP, Halliday GM. (2008) Acta Neuropathol. 2008 Dec;116(6):639-46
2008: Prof Tamas Revesz and Dr. Janice Holton, UCL Institute of Neurology, awarded £60,000 for a year study into ‘The role of p25a in Glial Cytoplasmic Inclusion’ formation.