RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus

on behalf of the RENEWAL Study Group

doi:https://doi.org/10.1186/s13195-022-01103-7

RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus

on behalf of the RENEWAL Study Group

Research output: Contribution to journal › Review article › Academic › peer-review

6 Citations (Scopus)

Abstract

Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson’s disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia.

Original language	English
Article number	169
Journal	Alzheimer's Research and Therapy
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/s13195-022-01103-7
Publication status	Published - 1 Dec 2022

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https://doi.org/10.1186/s13195-022-01103-7

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@article{48371a6b368e4592a39d2dc4e4ed1202,

title = "RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus",

abstract = "Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson{\textquoteright}s disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia.",

author = "O{\textquoteright}Brien, {John T.} and Leonidas Chouliaras and Janet Sultana and John-Paul Taylor and Clive Ballard and {on behalf of the RENEWAL Study Group} and Dag Aarsland and Frederic Blanc and Bradley Boeve and Brooks, {David J.} and Chaudhuri, {K. Ray} and Jeffrey Cummings and Feldman, {Howard H.} and Leon Flicker and Galvin, {James E.} and Grosset, {Donald G.} and Manabu Ikeda and Susan Kohlhaas and Brian Lawlor and Lemstra, {Afina W.} and Iracema Leroi and Elisabet Londos and Leverenz, {James B.} and Simon Lewis and Ian McKeith and Roger Mills and Richard Oakley and Jill Richardson and Marwan Sabbagh and John Skidmore and Per Svennigsson and Pietro Tiraboschi and Daniel Weintraub and Zuzana Walker and Rosie Watson and Weil, {Rimona S.} and Williams-Gray, {Caroline H.} and Alison Yarnall",

note = "Funding Information: This study was funded by a project grant from the UK Lewy Body Society. JOB is supported by the Cambridge NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). J-PT is supported by NIHR Newcastle Biomedical Research Centre based at Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Funding Information: RENEWAL Study Group (group authorship members): Dag Aarsland, Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King{\textquoteright}s College London, London, UK Frederic Blanc, ICube Laboratory UMR 7357 and FMTS (F{\'e}d{\'e}ration de M{\'e}decine Translationnelle de Strasbourg), IMIS team, University of Strasbourg and CNRS, Strasbourg, France. CM2R (Research and Resources Memory Centre), Geriatric Day Hospital and Cognitive-behavioural Unit, Geriatrics Department, University Hospitals of Strasbourg, Strasbourg, France. Bradley Boeve, Department of Neurology Mayo Clinic Rochester Minnesota USA. David J Brooks, Positron Emission Tomography Centre Newcastle University, Newcastle upon Tyne United Kingdom; Department of Nuclear Medicine and PET Centre Aarhus University Hospital Aarhus Denmark. K. Ray Chaudhuri, King{\textquoteright}s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience and Parkinson{\textquoteright}s Foundation Centre of Excellence, King{\textquoteright}s College Hospital, London, UK Jeffrey Cummings, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA. Howard H. Feldman, Dept. of Neurosciences, University of California San Diego (UCSD), San Diego, CA, USA, Alzheimer Disease Cooperative Study, UCSD, San Diego, CA, USA, Leon Flicker, Geriatric Medicine, Western Australian Centre for Health & Ageing, University of Western Australia, Royal Perth Hospital, Perth, Western Australia, Australia. James E Galvin, Comprehensive Center for Brain Health, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. Donald G Grosset, Institute of Neuroscience and Psychology, University of Glasgow, United Kingdom Manabu Ikeda, Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan. Susan Kohlhaas, Alzheimer{\textquoteright}s Research UK, Cambridge, UK Brian Lawlor, The Global Brain Health Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland. Afina W Lemstra, Department of Neurology, Alzheimer Center Amsterdam, Amsterdam University Medical Center, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. Iracema Leroi, Department of Psychiatry and The Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland. Elisabet Londos, Department of Clinical Sciences Malm{\"o}, Lund University, Lund, Sweden; Memory Clinic, Sk{\aa}ne University Hospital, Malm{\"o}, Sweden. James B. Leverenz, Lou Ruvo Center for Brain Health Neurological Institute Cleveland Clinic Cleveland Ohio USA Simon Lewis, Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, New South Wales, Australia. Ian McKeith, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK Roger Mills, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK; Vincere Consulting, LLC, San Diego, CA, USA. Richard Oakley, Alzheimer's Society UK, London, UK Jill Richardson, Neuroscience, Discovery Research, MSD, London, UK Marwan Sabbagh, Barrow Neurological Institute Phoenix, AZ, USA John Skidmore, ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, UK Per Svennigsson, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King{\textquoteright}s College Hospital, London, UK Pietro Tiraboschi, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133, Milan, Italy. Daniel Weintraub, Department of Psychiatry University of Pennsylvania, Philadelphia, Pennsylvania, USA. Zuzana Walker, Division of Psychiatry, University College London, London, UK; Essex Partnership University NHS Foundation Trust, Essex, UK Rosie Watson, Department of Medicine - The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. Rimona S. Weil, Dementia Research Centre, University College London, London, UK; Wellcome Centre for Human Neuroimaging, University College London, London, UK; Movement Disorders Consortium, National Hospital for Neurology and Neurosurgery, London, UK Caroline H. Williams-Gray, John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge, UK; Cambridge University Hospitals NHS Trust, Cambridge, UK. Alison Yarnall, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Faculty of Medical Sciences, Newcastle University, UK; Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "1",

doi = "https://doi.org/10.1186/s13195-022-01103-7",

language = "English",

volume = "14",

journal = "Alzheimer's Research and Therapy",

issn = "1758-9193",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - RENEWAL

T2 - REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus

AU - O’Brien, John T.

AU - Chouliaras, Leonidas

AU - Sultana, Janet

AU - Taylor, John-Paul

AU - Ballard, Clive

AU - on behalf of the RENEWAL Study Group

AU - Aarsland, Dag

AU - Blanc, Frederic

AU - Boeve, Bradley

AU - Brooks, David J.

AU - Chaudhuri, K. Ray

AU - Cummings, Jeffrey

AU - Feldman, Howard H.

AU - Flicker, Leon

AU - Galvin, James E.

AU - Grosset, Donald G.

AU - Ikeda, Manabu

AU - Kohlhaas, Susan

AU - Lawlor, Brian

AU - Lemstra, Afina W.

AU - Leroi, Iracema

AU - Londos, Elisabet

AU - Leverenz, James B.

AU - Lewis, Simon

AU - McKeith, Ian

AU - Mills, Roger

AU - Oakley, Richard

AU - Richardson, Jill

AU - Sabbagh, Marwan

AU - Skidmore, John

AU - Svennigsson, Per

AU - Tiraboschi, Pietro

AU - Weintraub, Daniel

AU - Walker, Zuzana

AU - Watson, Rosie

AU - Weil, Rimona S.

AU - Williams-Gray, Caroline H.

AU - Yarnall, Alison

N1 - Funding Information: This study was funded by a project grant from the UK Lewy Body Society. JOB is supported by the Cambridge NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). J-PT is supported by NIHR Newcastle Biomedical Research Centre based at Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Funding Information: RENEWAL Study Group (group authorship members): Dag Aarsland, Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK Frederic Blanc, ICube Laboratory UMR 7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS team, University of Strasbourg and CNRS, Strasbourg, France. CM2R (Research and Resources Memory Centre), Geriatric Day Hospital and Cognitive-behavioural Unit, Geriatrics Department, University Hospitals of Strasbourg, Strasbourg, France. Bradley Boeve, Department of Neurology Mayo Clinic Rochester Minnesota USA. David J Brooks, Positron Emission Tomography Centre Newcastle University, Newcastle upon Tyne United Kingdom; Department of Nuclear Medicine and PET Centre Aarhus University Hospital Aarhus Denmark. K. Ray Chaudhuri, King’s College London, Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience and Parkinson’s Foundation Centre of Excellence, King’s College Hospital, London, UK Jeffrey Cummings, Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA. Howard H. Feldman, Dept. of Neurosciences, University of California San Diego (UCSD), San Diego, CA, USA, Alzheimer Disease Cooperative Study, UCSD, San Diego, CA, USA, Leon Flicker, Geriatric Medicine, Western Australian Centre for Health & Ageing, University of Western Australia, Royal Perth Hospital, Perth, Western Australia, Australia. James E Galvin, Comprehensive Center for Brain Health, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA. Donald G Grosset, Institute of Neuroscience and Psychology, University of Glasgow, United Kingdom Manabu Ikeda, Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan. Susan Kohlhaas, Alzheimer’s Research UK, Cambridge, UK Brian Lawlor, The Global Brain Health Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland. Afina W Lemstra, Department of Neurology, Alzheimer Center Amsterdam, Amsterdam University Medical Center, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands. Iracema Leroi, Department of Psychiatry and The Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland. Elisabet Londos, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden. James B. Leverenz, Lou Ruvo Center for Brain Health Neurological Institute Cleveland Clinic Cleveland Ohio USA Simon Lewis, Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, New South Wales, Australia. Ian McKeith, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK Roger Mills, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK; Vincere Consulting, LLC, San Diego, CA, USA. Richard Oakley, Alzheimer's Society UK, London, UK Jill Richardson, Neuroscience, Discovery Research, MSD, London, UK Marwan Sabbagh, Barrow Neurological Institute Phoenix, AZ, USA John Skidmore, ALBORADA Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, UK Per Svennigsson, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College Hospital, London, UK Pietro Tiraboschi, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133, Milan, Italy. Daniel Weintraub, Department of Psychiatry University of Pennsylvania, Philadelphia, Pennsylvania, USA. Zuzana Walker, Division of Psychiatry, University College London, London, UK; Essex Partnership University NHS Foundation Trust, Essex, UK Rosie Watson, Department of Medicine - The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. Rimona S. Weil, Dementia Research Centre, University College London, London, UK; Wellcome Centre for Human Neuroimaging, University College London, London, UK; Movement Disorders Consortium, National Hospital for Neurology and Neurosurgery, London, UK Caroline H. Williams-Gray, John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge, UK; Cambridge University Hospitals NHS Trust, Cambridge, UK. Alison Yarnall, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Faculty of Medical Sciences, Newcastle University, UK; Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson’s disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia.

AB - Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson’s disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia.

UR - http://www.scopus.com/inward/record.url?scp=85141703044&partnerID=8YFLogxK

U2 - https://doi.org/10.1186/s13195-022-01103-7

DO - https://doi.org/10.1186/s13195-022-01103-7

M3 - Review article

C2 - 36369100

SN - 1758-9193

VL - 14

JO - Alzheimer's Research and Therapy

JF - Alzheimer's Research and Therapy

IS - 1

M1 - 169

ER -

RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus

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