Efficacy and safety of low-dose IL-2 (ld-IL-2) as a Treg enhancer for anti-neuroinflammatory therapy in newly diagnosed Amyotrophic Lateral Sclerosis (ALS) patients

Deliverables

Approval from IRBs and Regulatory Agencies

All approval documents to start patient recruitment.

International workshops

Prospect and impact of IL2 in ALS management and New design for clinical trials in neurodegenerative diseases

Corporate communication tools provided

Logo, brochure, public website

Publications

The involvement of regulatory T cells in amyotrophic lateral sclerosis and their therapeutic potential

Author(s): I. Giovannelli, P. Heath, P. J. Shaw, J. Kirby
Published in: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Issue 21/5-6, 2020, Page(s) 435-444, ISSN 2167-8421
Publisher: Informa Healthcare
DOI: 10.1080/21678421.2020.1752246

A Knowledge-Based Machine Learning Approach to Gene Prioritisation in Amyotrophic Lateral Sclerosis

Author(s): Daniel Bean; Daniel Bean; Ammar Al-Chalabi; Ammar Al-Chalabi; Richard Dobson; Richard Dobson; Alfredo Iacoangeli
Published in: Genes, Vol 11, Iss 668, p 668 (2020), Issue 20734425, 2020, ISSN 2073-4425
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/genes11060668

Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics

Author(s): Arvin Behzadi; Fani Pujol-Calderón; Anton Tjust; Anna Wuolikainen; Kina Höglund; Kina Höglund; Karin Forsberg; Erik Portelius; Erik Portelius; Kaj Blennow; Kaj Blennow; Henrik Zetterberg; Peter M. Andersen
Published in: Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021), Issue 20452322, 2021, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-021-01499-6

ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS

Author(s): Crockford, Christopher; Newton, Judith; Lonergan, Katie; Chiwera, Theresa; Booth, Tom; Chandran, Siddharthan; Colville, Shuna; Heverin, Mark; Mays, Iain; Pal, Suvankar; Pender, Niall; Pinto-Grau, Marta; Radakovic, Ratko; Shaw, Christopher E.; Stephenson, Laura; Swingler, Robert; Vajda, Alice; Al-Chalabi, Ammar; Hardiman, Orla; Abrahams, Sharon
Published in: Crockford , C , Newton , J , Lonergan , K , Chiwera , T , Booth , T , Chandran , S , Colville , S , Heverin , M , Mays , I , Pal , S , Pender , N , Pinto-Grau , M , Radakovic , R , Shaw , C E , Stephenson , L , Swingler , R , Vajda , A , Al-Chalabi , A , Hardiman , O & Abrahams , S 2018 , ' ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS ' , Neurology , v, Issue 1, 2018, ISSN 0028-3878
Publisher: Lippincott Williams & Wilkins Ltd.

A survey of current practices

Author(s): Vajda, Alice; McLaughlin, Russell L.; Heverin, Mark; Thorpe, Owen; Abrahams, Sharon; Al-Chalabi, Ammar; Hardiman, Orla
Published in: Neurology, Issue 6, 2017, ISSN 0028-3878
Publisher: Lippincott Williams & Wilkins Ltd.

Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis

Author(s): Ahmad Al Khleifat; Alfredo Iacoangeli; Joke J. F. A. van Vugt; Harry Bowles; Matthieu Moisse; Ramona A. J. Zwamborn; Rick A. A. van der Spek; Aleksey Shatunov; Johnathan Cooper-Knock; Simon Topp; Ross Byrne; Cinzia Gellera; Victoria López; Ashley R. Jones; Sarah Opie-Martin; Atay Vural; Yolanda Campos; Wouter van Rheenen; Brendan Kenna; Kristel R. Van Eijk; Kevin Kenna; Markus Weber; Bradley Smit
Published in: NPJ Genomic Medicine, Issue 20567944, 2022, ISSN 2056-7944
Publisher: Springer Nature
DOI: 10.1038/s41525-021-00267-9

DGLinker: flexible knowledge-graph prediction of disease–gene associations

Author(s): Jiajing Hu; Rosalba Lepore; Richard Dobson; Richard Dobson; Ammar Al-Chalabi; Ammar Al-Chalabi; Daniel Bean; Daniel Bean; Alfredo Iacoangeli; Alfredo Iacoangeli
Published in: Nucleic Acids Research, Issue 03051048, 2021, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gkab449

Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): A phase 2a randomised, double-blind, placebo-controlled trial

Author(s): William Camu, Marius Mickunas, Jean-Luc Veyrune, Christine Payan, Cecilia Garlanda, Massimo Locati, Raul Juntas-Morales, Nicolas Pageot, Andrea Malaspina, Ulf Andreasson, Janine Kirby, Carey Suehs, Safa Saker, Christophe Masseguin, John De Vos, Henrik Zetterberg, Pamela J Shaw, Ammar Al-Chalabi, P Nigel Leigh, Timothy Tree, Gilbert Bensimon
Published in: EBioMedicine, Issue 59, 2020, Page(s) 102844, ISSN 2352-3964
Publisher: Elsevier BV
DOI: 10.1016/j.ebiom.2020.102844

The genetics of amyotrophic lateral sclerosis: current insights

Author(s): Janine Kirby, Afnan Al Sultan, Rachel Waller, Paul Heath
Published in: Degenerative Neurological and Neuromuscular Disease, 2016, Page(s) 49, ISSN 1179-9900
Publisher: Dove Press
DOI: 10.2147/dnnd.s84956

A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK

Author(s): Sarah Morgan, Aleksey Shatunov, William Sproviero, Ashley R. Jones, Maryam Shoai, Deborah Hughes, Ahmad Al Khleifat, Andrea Malaspina, Karen E. Morrison, Pamela J. Shaw, Christopher E. Shaw, Katie Sidle, Richard W. Orrell, Pietro Fratta, John Hardy, Alan Pittman, Ammar Al-Chalabi
Published in: Brain, Issue 140/6, 2017, Page(s) 1611-1618, ISSN 0006-8950
Publisher: Oxford University Press
DOI: 10.1093/brain/awx082

Genetic testing in ALS

Author(s): Alice Vajda, Russell L. McLaughlin, Mark Heverin, Owen Thorpe, Sharon Abrahams, Ammar Al-Chalabi, Orla Hardiman
Published in: Neurology, Issue 88/10, 2017, Page(s) 991-999, ISSN 0028-3878
Publisher: Lippincott Williams & Wilkins Ltd.
DOI: 10.1212/WNL.0000000000003686

Detection of long repeat expansions from PCR-free whole-genome sequence data

Author(s): Egor Dolzhenko, Joke J.F.A. van Vugt, Richard J. Shaw, Mitchell A. Bekritsky, Marka van Blitterswijk, Giuseppe Narzisi, Subramanian S. Ajay, Vani Rajan, Bryan R. Lajoie, Nathan H. Johnson, Zoya Kingsbury, Sean J. Humphray, Raymond D. Schellevis, William J. Brands, Matt Baker, Rosa Rademakers, Maarten Kooyman, Gijs H.P. Tazelaar, Michael A. van Es, Russell McLaughlin, William Sproviero, Aleksey Sha
Published in: Genome Research, Issue 27/11, 2017, Page(s) 1895-1903, ISSN 1088-9051
Publisher: Cold Spring Harbor Laboratory Press
DOI: 10.1101/gr.225672.117

Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study

Author(s): Ton Fang, Ahmad Al Khleifat, Jacques-Henri Meurgey, Ashley Jones, P Nigel Leigh, Gilbert Bensimon, Ammar Al-Chalabi
Published in: The Lancet Neurology, Issue 17/5, 2018, Page(s) 416-422, ISSN 1474-4422
Publisher: The Lancet Publishing Group
DOI: 10.1016/S1474-4422(18)30054-1

Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases

Author(s): Jason A. Chen, Zhongbo Chen, Hyejung Won, Alden Y. Huang, Jennifer K. Lowe, Kevin Wojta, Jennifer S. Yokoyama, Gilbert Bensimon, P. Nigel Leigh, Christine Payan, Aleksey Shatunov, Ashley R. Jones, Cathryn M. Lewis, Panagiotis Deloukas, Philippe Amouyel, Christophe Tzourio, Jean-Francois Dartigues, Albert Ludolph, Adam L. Boxer, Jeff M. Bronstein, Ammar Al-Chalabi, Daniel H. Geschwind, Giovanni Cop
Published in: Molecular Neurodegeneration, Issue 13/1, 2018, ISSN 1750-1326
Publisher: BioMed Central
DOI: 10.1186/s13024-018-0270-8

The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison

Author(s): Sarah Martin, Emma Trevor-Jones, Sabyha Khan, Keelan Shaw, Deepti Marchment, Anna Kulka, Catherine E Ellis, Rachel Burman, Martin R. Turner, Liam Carroll, Leah Mursaleen, P. Nigel Leigh, Christopher E. Shaw, Neil Pearce, Daniel Stahl, Ammar Al-Chalabi
Published in: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Issue 18/7-8, 2017, Page(s) 569-575, ISSN 2167-8421
Publisher: Informa Healthcare
DOI: 10.1080/21678421.2017.1349151

Proposed association between the hexanucleotide repeat of C9orf72 and opposability index of the thumb

Author(s): Zhongbo Chen, Kuang Lin, Jeffrey D. Macklis, Ammar Al-Chalabi
Published in: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Issue 18/3-4, 2017, Page(s) 175-181, ISSN 2167-8421
Publisher: Informa Healthcare
DOI: 10.1080/21678421.2016.1257024

ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function

Author(s): Martina de Majo, Simon D. Topp, Bradley N. Smith, Agnes L. Nishimura, Han-Jou Chen, Athina Soragia Gkazi, Jack Miller, Chun Hao Wong, Caroline Vance, Frank Baas, Anneloor L.M.A. ten Asbroek, Kevin P. Kenna, Nicola Ticozzi, Alberto Garcia Redondo, Jesús Esteban-Pérez, Cinzia Tiloca, Federico Verde, Stefano Duga, Karen E. Morrison, Pamela J. Shaw, Janine Kirby, Martin R. Turner, Kevin Talbot, Orla
Published in: Neurobiology of Aging, Issue 71, 2018, Page(s) 266.e1-266.e10, ISSN 0197-4580
Publisher: Elsevier BV
DOI: 10.1016/j.neurobiolaging.2018.06.015

Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis

Author(s): Jeremy A. Garson, Louise Usher, Ammar Al-Chalabi, Jim Huggett, Edmund F. Day, Adele L. McCormick
Published in: Acta Neuropathologica Communications, Issue 7/1, 2019, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-019-0698-2

Telomere length is greater in ALS than in controls: a whole genome sequencing study

Author(s): Ahmad Al Khleifat, Alfredo Iacoangeli, Aleksey Shatunov, Ton Fang, William Sproviero, Ashley R. Jones, Sarah Opie-Martin, Karen E. Morrison, Pamela J. Shaw, Christopher E. Shaw, John F. Powell, Richard Dobson, Steven J. Newhouse, Ammar Al-Chalabi
Published in: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Issue 20/3-4, 2019, Page(s) 229-234, ISSN 2167-8421
Publisher: Informa Healthcare
DOI: 10.1080/21678421.2019.1586951

DNAscan: personal computer compatible NGS analysis, annotation and visualisation

Author(s): A. Iacoangeli, A. Al Khleifat, W. Sproviero, A. Shatunov, A. R. Jones, S. L. Morgan, A. Pittman, R. J. Dobson, S. J. Newhouse, A. Al-Chalabi
Published in: BMC Bioinformatics, Issue 20/1, 2019, ISSN 1471-2105
Publisher: BioMed Central
DOI: 10.1186/s12859-019-2791-8

C9orf72 intermediate expansions of 24–30 repeats are associated with ALS

Author(s): Alfredo Iacoangeli, Ahmad Al Khleifat, Ashley R. Jones, William Sproviero, Aleksey Shatunov, Sarah Opie-Martin, Karen E. Morrison, Pamela J. Shaw, Christopher E. Shaw, Isabella Fogh, Richard J. Dobson, Stephen J. Newhouse, Ammar Al-Chalabi
Published in: Acta Neuropathologica Communications, Issue 7/1, 2019, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-019-0724-4

Younger age of onset in familial amyotrophic lateral sclerosis is a result of pathogenic gene variants, rather than ascertainment bias.

Author(s): Mehta, P.R.; Jones, A.R.; Opie-Martin, S.; Shatunov, A.; Iacoangeli, A.; Al Khleifat, A.; Smith, B.N.; Topp, S.; Morrison, K.E.; Shaw, P.J.; Shaw, C.E.; Morgan, S.; Pittman, A.; Al-Chalabi, A.
Published in: 0022-3050, Issue 1, 2018, ISSN 0022-3050
Publisher: BMJ Publishing Group

Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020–2116

Author(s): Alison Gowland; Sarah Opie-Martin; Kirsten M. Scott; Ashley R. Jones; Puja Mehta; Christine J. Batts; C M Ellis; P. Nigel Leigh; Christopher Shaw; Jemeen Sreedharan; Ammar Al-Chalabi
Published in: 2167-9223, Issue 21678421, 2019, ISSN 2167-8421
Publisher: Informa Healthcare
DOI: 10.6084/m9.figshare.7969733.v1

Elongator subunit 3 (ELP3) modifies ALS through tRNA modification

Author(s): André Bento-Abreu; Gunilla Jäger; Bart Swinnen; Laura Rué; Stijn Hendrickx; Ashley R. Jones; Kim A. Staats; Ines Taes; Caroline Eykens; Annelies Nonneman; Rik Nuyts; Mieke Timmers; Lara Silva; Alain Chariot; Laurent Nguyen; John Ravits; Robin Lemmens; Deirdre Cabooter; Ludo Van Den Bosch; Philip Van Damme; Ammar Al-Chalabi; Anders S. Byström; Wim Robberecht
Published in: Bento-Abreu , A , Jager , G , Swinnen , B , Rué , L , Hendrickx , S , Jones , A , Staats , K A , Taes , I , Eykens , C , Nonneman , A , Nuyts , R , Timmers , M , Silva , L , Chariot , A , Nguyen , L , Ravits , J , Lemmens , R , Cabooter , D , Van Den Bosch , L , Van Damme , P , Al-Chalabi , A , Bystrom , A & Robberecht , W 2018 , ' Elongator subunit 3 (ELP3) modifies ALS through tRNA modification, Issue 09646906, 2018, ISSN 0964-6906
Publisher: Oxford University Press
DOI: 10.1093/hmg/ddy043

Relative preservation of triceps over biceps strength in upper limb-onset ALS: the ‘split elbow’

Author(s): Roaya Khalaf; Sarah Martin; C M Ellis; Rachel Burman; Jemeen Sreedharan; Christopher Shaw; P. Nigel Leigh; Martin R Turner; Ammar Al-Chalabi
Published in: 0022-3050, Issue 00223050, 2019, ISSN 0022-3050
Publisher: BMJ Publishing Group
DOI: 10.1136/jnnp-2018-319894

Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2

Author(s): Ilaria Giovannelli, Nadhim Bayatti, Abigail Brown, Dennis Wang, Marius Mickunas, William Camu, Jean-Luc Veyrune, Christine Payan, Cecilia Garlanda, Massimo Locati, Raul Juntas-Morales, Nicolas Pageot, Andrea Malaspina, Ulf Andreasson, Carey Suehs, Safa Saker, Christophe Masseguin, John de Vos, Henrik Zetterberg, Ammar Al-Chalabi, P Nigel Leigh, Timothy Tree, Gilbert Bensimon, Paul R Heath, Pamela
Published in: Brain Communications, 2021, ISSN 2632-1297
Publisher: Oxford University Press
DOI: 10.1093/braincomms/fcab141

Occasional essay: Upper motor neuron syndrome in amyotrophic lateral sclerosis.

Author(s): Michael Swash; Michael Swash; David Burke; Martin R Turner; Julian Grosskreutz; P. Nigel Leigh; Mamede deCarvalho; Matthew C. Kiernan; Matthew C. Kiernan
Published in: 0022-3050, 2019
Publisher: BMJ
DOI: 10.1136/jnnp-2019-321938

Retrotransposons in the development and progression of amyotrophic lateral sclerosis

Author(s): Savage, Abigail L; Schumann, Gerald G; Breen, Gerome; Bubb, Vivien J; Al-Chalabi, Ammar; Quinn, John P
Published in: Journal of Neurology, Neurosurgery, and Psychiatry, 2018
Publisher: BMJ